Prostate Cancer

Review Identifies Factors That Influence Patient Treatment Choice For Localized Prostate Cancer

2007-05-07T10:06:00.001-07:00

UroToday.com - Variables that influence a patients' choice of treatment for localized prostate cancer (CaP) are identified in a literature review that is authored by Dr. Zeliadt and colleagues and appears in the on-line version of Cancer, 2006.

Cancer eradication is a primary concern for many men, but perhaps surprisingly not paramount to all patients. One study of 1000 CaP patients found that 42% defined an effective treatment as one that extended survival or delayed disease progression, but 45% defined effectiveness as preservation of quality of life (QOL). This contrasted to physicians, of whom 90% defined effectiveness as extended survival. In another study, only 20% of CaP patients selected either "effect of treatment of length of life" or "chances of dying of cancer" as 1 of the 4 most relevant factors in making a decision.

It is apparent that CaP patients associate cancer eradication with aggressiveness of therapy and radical prostatectomy (RP) was considered the most aggressive. One study found that 98% of RP patients and 50% of brachytherapy patients selected their treatment choice on the basis of evidence that it was the most curative procedure.

Regarding QOL, the issue of incontinence was more concerning than impotence. In fact, urinary and bowel side effects were the only 2 variables found to be important to greater than 50% of patients. Another study found that 49% and 38% of patients were concerned about incontinence and impotence, respectively. However, this must be assessed in the context of their pre-operative functional status. One report found that 55% of spouses reported that side effects were important, but only 6% indicated that side effects were deciding factors.

Only 2% of men indicated that out-of-pocket costs were important in selecting treatment choice. While spouses often are very involved in obtaining treatment information, one study found that only 13% of patients thought they would base their decision on family influence.

Clearly, patients are more involved in the decision making process. The same survey given to 2 cohorts of patients 5 years apart finds that more recently 32% as compared to 58% wanted their physician to make the final decision. Also, patients most commonly rely on the opinion of their urologist. While 37% sought a second opinion, 75% selected the first treatment recommended to them.

Review of studies regarding racial, socioeconomic and cultural factors reveal that African-American men more commonly receive less aggressive therapy. However, more educated men more commonly had watchful waiting presented to them, while higher income patients had surgery or brachytherapy discussed.

Many variables are found to influence a patients' selection of treatment for localized CaP. In addition to cancer eradication and QOL, clearly the initial physician a CaP patient interacts with regarding their new diagnosis of CaP is the most influential.

By Christopher P. Evans, MD

Reference:
Cancer. 2006 May 1;106(9):1865-74.
Link Here. Zeliadt SB, Ramsey SD, Penson DF, Hall IJ, Ekwueme DU, Stroud L, Lee JW

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Common Genetic Prostate Cancer Variant Is Identified

2007-05-07T09:06:00.001-07:00

UroToday.com - Prostate cancer (CaP) is a presumed result of both genetic and environmental events. It is known that a positive family history and African-American ancestry will increase the risk of developing CaP 2-4 fold. This strongly supports a genetic alteration as a significant contributing factor. In the online version of Nature Genetics, the group working under Dr. Kari Stefansson in Iceland has reported a genetic variant on chromosome 8q24.

In the report, 3 genome-wide linkage studies were performed. The first used 1.068 microsatellite markers (repetitive stretches of short DNA sequences that occur in increased numbers in cancer cells) were typed for 871 Icelandic men with CaP that grouped into 323 extended families. This identified a suggestive linkage signal on chromosome 8q24. The researchers genotyped an additional 358 microsatellite markers spanning this region in 869 unrelated men with CaP and 596 population case-controls.

A second group of 422 Icelandic men with CaP and 401 controls was studied and the -8 variant was verified with an OR of 1.72 (p=0.0018). Combining the Icelandic groups demonstrated that the DG8S737 -8 allele variant had a frequency of 13.1% in affected men and 7.8% in controls. This corresponded to a population attributable risk of 11%.

Furthermore, 63 single nucleotide pleomorphisms (SNPs or single nucleotide alterations in a short genetic sequence) were geontyped and 37 were found significantly associated with CaP. Most associated were allele A of SNP rs1447295 (OR=1.72) and this correlated with the DG8S737 -8 allele.

The researchers attempted to replicate the findings in 1.435 unrelated men with CaP and 779 controls from Sweden and 458 European America men with CaP and 247 controls from Chicago. The frequency of the DG8S737 -8 allele variant was greater in affected men than in controls for all groups.

In the final study, 246 African-American men with CaP and 352 controls were genotyped and the frequency of the DG8S737 -8 allele variant was 23.4% in African American men with CaP and 16.1% in controls with an OR of 1.6. Of the SNPs evaluated in this study, rs1447295 gave the lowest, but not significant result suggesting that DG8S737 -8 rather than the SNPs is either itself a functional variant or is tightly associated with a presently unknown risk variant. In African-American men the association for affected individuals was 41% and 30% in the population, with a population attributable risk of 16% that may contribute to the higher incidence of CaP in African-American men.

An analysis of 510 Icelandic men with BPH did not show a significant excess of either the DG8S737 -8 allele or allele A of re1447295.

By Christopher P. Evans, MD

Reference:
Nat Genet. 2006 Jun;38(6):652-8. Epub 2006 May 7.
Link Here (PDF)

Amundadottir LT, Sulem P, Gudmundsson J, Helgason A, Baker A, Agnarsson BA, Sigurdsson A, Benediktsdottir KR, Cazier JB, Sainz J, Jakobsdottir M, Kostic J, Magnusdottir DN, Ghosh S, Agnarsson K, Birgisdottir B, Le Roux L, Olafsdottir A, Blondal T, Andresdottir M, Gretarsdottir OS, Bergthorsson JT, Gudbjartsson D, Gylfason A, Thorleifsson G, Manolescu A, Kristjansson K, Geirsson G, Isaksson H, Douglas J, Johansson JE, Balter K, Wiklund F, Montie JE, Yu X, Suarez BK, Ober C, Cooney KA, Gronberg H, Catalona WJ, Einarsson GV, Barkardottir RB, Gulcher JR, Kong A, Thorsteinsdottir U, Stefansson K

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Establishing An Integrated Molecular Signature Model For Metastatic Prostate Cancer

2007-05-07T08:06:00.001-07:00

UroToday.com - Genomic and proteomic profiling has attempted to link patients with the likelihood for advanced disease progression. Approaches to do this are reviewed by Dr. Taylor and associates in the June 1, 2006 issue of Cancer Research.

Integrated approaches are of three types. One uses data available in the public domain rather than experimental, patient derived data and uses data-mining and bioinformatics. A second model integrates experimental data with heterogeneous public data sources. The third approach integrates multifaceted genomic and proteomic data for analysis of metastatic risk.

The paper reviews the integrated approach from the laboratory of Dr. Arul Chinnaiyan at the University of Michigan. Specimens from patients include benign, localized malignant and metastatic tissues that undergo direct proteomic analysis by an antibody-based high-throughput immunoblot approach. This methodology was validated with traditional immunoblotting and tissue microarray-based immunohistochemical staining. Correlation was also performed with prostate cancer transcriptomes to include publicly available genes expression studies and microarrays. Mapping between genes and dysregulated proteins resulted in data for meta-analysis by statistical procedures.

A 50-gene ensemble was identified that served as a multiplex signature of CaP progression when it was applied to patient primary disease specimens. The 50-gene signature was tested with two CaP gene expression studies and demonstrated strong concordance. The data suggests that mRNA transcripts that correlate with protein levels in metastatic disease could be applied as a multiplex gene predictor of CaP progression in localized disease. Application to other primary tumor types also supported relevance.

The integration of high-throughput data could also be extended to other proteomic platforms, such as mass spectrometry or array-based platforms.

By Christopher P. Evans, MD

Reference:
Cancer Res 2006;66:5537-39
Link Here.
Taylor BS, Varambally S, Chinnaiyan AM

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Symptom Severity Of PBS/IC Difficult To Predict Based On Medical History And Demographics

2007-05-07T07:07:00.001-07:00

UroToday.com - The association, if any, between medical or demographic characteristics and symptom severity in chronic prostatitis/ chronic pelvic pain syndrome (CP/CPPS) and PBS/IC patients has not been well studied. Clemens and colleagues from Northwestern University reviewed their patient database covering 1999 to 2002 to identify patients diagnosed with CP/CPPS and IC. Questionnaires were mailed to these patients, and nonresponders were followed up 6 months later. The questionnaires asked for information on demographics, medical history, and smoking and alcohol intake. A standardized mental health questionnaire was administered, and females were sent the O'Leary Sant Symptom and Problem Indexes as well as the AUA Symptom Index. Men were sent the NIH chronic prostatitis symptom index.

Self-reported urinary urgency and frequency, depression and lower education level were independent predictors of symptom severity in men with CP/CPPS and women with PBS/IC. Self-reported pelvic pain, fibromyalgia and a previous heart attack predicted symptom severity in men and postmenopausal status predicted symptom severity in women. The authors conclude that although several common medical conditions are associated with urological pelvic pain syndromes in men women, few of them were predictive of symptom severity in this analysis.

By Philip M Hanno, MD, MPH
Reference:
Journal of Urology, 175:963-967, 2006
Link Here.
Clemens JQ, Brown SO, Kozloff L, Calhoun EA

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Time To Prostate Specific Antigen Recurrence After Radical Prostatectomy And Risk Of Prostate Cancer Specific Mortality

2007-04-16T17:15:00.001-07:00

UroToday.com - Aside from preoperative PSA, Gleason score, and pathologic stage, surrogate markers for prostate cancer-related death after prostatectomy include PSA doubling time and the length of time from surgery to PSA recurrence.

In the October issue of the Journal of Urology, Freedland and co-workers from Johns Hopkins performed a detailed analysis of a contemporary series of 379 patients who developed disease recurrence after radical prostatectomy.

The authors found that disease-specific survival significantly decreased if the PSA recurrence occurred 3 years after surgery, with a hazard ratio of 2.70 (95% confidence interval, 1.37 to 5.31, p = 0.004). The 15-year estimated survival for patients with disease recurrence less than 3 years after surgery was 41% (95% CI 29 to 53) compared to 87% in those with recurrence 3 years after prostatectomy.

These data provide additional evidence that PSA recurrence within 3 years of surgery may serve as a surrogate marker for prostate cancer death. Most importantly, this information provides reassurance that the majority of patients with surgically-treated prostate cancer who recur after 3 years will not die of their disease.

J Urol. 2006 Oct;176(4 Pt 1):1404-1408.
Reviewed By UroToday.com Contributing Editor Ricardo F. SГЎnchez-Ortiz, MD

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Statin Use Associated With Decreased Risk Of Advanced Prostate Cancer

2007-04-16T16:35:00.001-07:00

Use of cholesterol-lowering medications called statins is not associated with a lower risk of prostate cancer overall, but it is associated with a decreased risk of advanced disease, a large prospective study finds.

Two recently reported studies found an association between statin use and a reduced risk of prostate cancer. However, other observational studies and clinical trials have not confirmed those findings.

To investigate a possible association between statin use and the risk of prostate cancer and advanced prostate cancer, Elizabeth A. Platz, Sc.D., of the Johns Hopkins Bloomberg School of Public Health in Baltimore, Md., and colleagues analyzed data from the Health Professionals Follow-up Study, a cohort of 34,989 U.S. men ages 40 to 75. From 1990 to 2002, the men were asked every other year about several factors, including use of cholesterol-lowering drugs.

In 1990, 4.4% of the men reported taking statins. By 2000, that number increased to 23.8%. Current statin use was not associated with risk of prostate cancer overall or of localized disease. However, current use of statins was associated with a reduced risk of advanced prostate cancer. Compared with men who had never taken statins, men currently taking statins had half the risk of advanced disease and less than half the risk of metastatic or fatal disease. The authors calculated that the incidence of advanced prostate cancer among current statin users was 38 cases per 100,000 men per year, and 89 cases per 100,000 men per year among nonusers. The inverse association was even stronger for metastatic and fatal prostate cancers combined, and the reduced risk of advanced disease was even lower with longer use of statins.

A possible confounding factor of the study is that more statin users than nonusers reported undergoing prostate-specific antigen (PSA) screening, a test often used as an early indicator of prostate cancer. Men who underwent multiple PSA tests were more likely to be diagnosed with localized prostate cancer and less likely to be diagnosed with advanced disease. The authors calculated that PSA screening did not account for their results, but they caution that it may have been a source of bias in the analysis.

"- It is premature to recommend the use of statins for the prevention of advanced prostate cancer," the authors write. "Further work is needed to address the role of PSA screening as a possible explanation for these findings and to identify the biologic mechanisms that may underlie the inverse association, if this association is indeed causal."

Contact: Vanessa Wasta, Johns Hopkins Kimmel Cancer Center Office of Public Affairs

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Other highlights in the December 20 JNCI

Note: The Journal of the National Cancer Institute is published by Oxford University Press and is not affiliated with the National Cancer Institute. Attribution to the Journal of the National Cancer Institute is requested in all news coverage. Visit the Journal online at http://jncicancerspectrum.oxfordjournals.org/.

Contact: Andrea Widener
Journal of the National Cancer Institute

Mucinous Adenocarcinoma Of The Prostate Does Not Confer Poor Prognosis

2007-04-16T15:15:00.001-07:00

UroToday.com - While mucinous adenocarcinoma of the colon and breast demonstrate poor and favorable prognoses, respectively, the clinical behavior of mucinous adenocarcinoma of the prostate (MC) is unknown. A report by Dr. Lane and associates at the Cleveland Clinic suggest that the clinical course of MC is similar to conventional prostate adenocarcinoma (AC). This paper appears in the October 2006 issue of Urology.

Between 1987 and 2005, complete data on 2,572 radical prostatectomy (RP) patients who did not receive adjuvant therapy was available for analysis. A total of 32 cases were identified: 14 with MC and 18 with AC with focal mucin (AFM). Pathological and clinical variables were correlated with outcomes. All pathology was re-reviewed by a single pathologist.

In the MC cohort, pathologic Gleason score was 6 in one, 7 in 4, and 8 in three patients. In 6 patients it was not evaluable due to neoadjuvant hormonal therapy. Non-organ confined disease was present in 12 (37.5%) with MC or AFM including 12 with extraprostatic extension, 6 with positive surgical margins, and 4 with seminal vesicle invasion. One-half of patients had a pelvic lymphadenectomy and none had metastatic disease. There was no statistically significant difference between the patients with MC, AFM or AC with regard to PSA levels, clinical T stage, biopsy or pathologic Gleason score, or non-organ confined disease.

In follow-up, 26 patients had at least 2 follow-up PSA tests. Of these 26 men, biochemical failure occurred in 1 patient with MC and 5 patients with AFM (23%) at a median of 4.2 years. Overall survival showed no statistical difference among those with MC, AFM or AC. The 5-year overall survival rate was 100%, 100%, and 96.6%, for those with MC, AFM or AC, respectively. The overall 5-year biochemical recurrence-free survival rate was 100%, 69.2%, and 77.8%, for those with MC, AFM or AC, respectively.

This data is the largest known series of MC patients and suggests that MC can be treated in a fashion similar to AC.

Urol 2006;68:825-830

Reviewed By UroToday.com Contributing Editor Christopher P. Evans, M.D

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Study Suggests Role For Y Chromosome In Prostate Cancer

2007-04-16T14:35:00.001-07:00

A new study finds that, among a group of men in Israel, men with only daughters had a 40 percent higher risk of prostate cancer than men with at least one son. The study raises the possibility that some mutation or variant on the Y chromosome may be involved in prostate cancer.

Although several studies have identified risk factors for prostate cancer and found some gene mutations that are associated with the disease, none of these can account for large numbers of prostate cancer cases. Some studies have suggested that prostate cancer risk may be associated with alterations on the X or Y chromosomes.

Because alterations on the sex chromosomes might affect the probability of having sons or daughters, Susan Harlap, M.D., of Columbia University in New York, decided to study cancer incidence and offspring among men participating in the Jerusalem Perinatal Study. During the study period, 712 men were diagnosed with prostate cancer. Compared with men who had at least one son, men with only daughters had a 40 percent increased risk of prostate cancer. Men with no daughters had no increase or decrease in prostate cancer risk compared with men with offspring of both sexes.

"Overall, our findings are consistent with hypotheses that tie Y chromosome loci to prostate cancer, although other explanations cannot be excluded," they write.

Contact: Stephanie Berger; Columbia University Office of Public Affairs

###

Other highlights in the January 3 JNCI

Note: The Journal of the National Cancer Institute is published by Oxford University Press and is not affiliated with the National Cancer Institute. Attribution to the Journal of the National Cancer Institute is requested in all news coverage. Visit the Journal online at http://jncicancerspectrum.oxfordjournals.org/.

Contact: Andrea Widener
Journal of the National Cancer Institute

Androgen Deprivation In Veterans With Prostate Cancer: Implications For Skeletal Health

2007-04-16T13:09:00.001-07:00

UroToday.com- In addition to prostate cancer (CaP) patients with metastatic disease, androgen-deprivation therapy (ADT) is increasingly used for patients with non-metastatic recurrent disease. This means that the long-term consequences of ADT to include bone loss are more likely. Patients on ADT may also have other risk factors for bone loss to include alcohol abuse, smoking, prior fracture or a propensity for bone trauma secondary to falling. In the online version of the Annals of Pharmacotherapy, Dr. Wilcox and associates evaluated skeletal health in a population of Veterans on ADT at the Minnesota VA. They proposed three hypotheses; that fracture risk factors in addition to ADT would exist in most of these patients, bone mass measurements would be performed in a minority, and a minority of patients would receive bisphosphonate therapy.

Veterans over age 50 years who received ADT between 1993 and 2001 were identified through VA pharmacy service records. Medical records of these men were then reviewed. Of the 351 patients identified, 174 met study criteria. Median duration of ADT was 21 months and 57% received LHRH monotherapy without an anti-androgen. Additional skeletal risk factors were identified in 81% and smoking, alcohol use and prior fracture were most common.

Of the 174 men, only 22 (13%) had bone mineral density measurement (BMD) performed. Seven of these 22 men had BMD prior to initiation of treatment and 5 were found to be osteoporotic. The other 15 had BMD testing after initiation of ADT and 8 were osteoporotic after beginning ADT (median time 29 months). Fewer than half of the men received either calcium or vitamin D supplements for skeletal health and only 11% received antiresorptive therapy. Seventeen of the 22 men who had BMD measured received antiresorptive therapy. Fractures occurred in 24 men, most commonly vertebrae and hip. In those with fractures, 11 had one other risk factor for osteoporosis in addition to ADT. Only 6 of the patients with fractures were on antiresorptive therapy. The fracture rate was not different between men on combined androgen blockade or monotherapy.

This study found that in their population of Veterans on ADT, skeletal risk factors existed in 80%, BMD was infrequently measured and only 11% received antiresorptive therapy. Unfortunately, the analysis did not seem to determine whether patients were started on ADT for metastatic disease or non-metastatic disease. In the 24 men who experienced a fracture, the duration of their ADT prior to the fracture and whether the fracture was associated with a metastatic site on imaging was not reported.

Andrew Wilcox, Molly L Carnes, Timothy D Moon, Renee Tobias, Heather Baade, Emily Stamos, and Mary E Elliott
Annals of Pharmacotherapy 2006: 40: 2107 - 2114

Reviewed by UroToday.com Contributing Editor Christopher P. Evans, M.D.

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The Natural History Of Noncastrate Metastatic Prostate Cancer After Radical Prostatectomy

2007-04-16T12:29:00.001-07:00

UroToday.com- Most patients with a rising PSA following relapse after primary therapy are treated with early androgen deprivation therapy (ADT). The natural history of these men therefore is not well defined. In the online version of European Urology, Dr. Yossepowitch and colleagues from Memorial Sloan-Kettering Cancer Center report that the median disease-specific survival from diagnosis of noncastrate metastases is 6.6 years.

The study cohort was comprised of 95 patients who developed metastatic disease without previously being treated by ADT for PSA relapse. Of these, 34 had received a short course of ADT before surgery, but testosterone was above castrate level at the time of metastatic presentation. Median follow-up was 7.1 years. Follow-up consisted of routine examinations, PSA testing, bone scans and additional imaging as indicated. At completion of follow-up, 33 men (35%) had died and in 29 of these the death was attributed to progressive castrate metastatic prostate cancer.

The mean interval from surgery to first evidence of metastatic disease was 4.2 years. Median PSA level at initial noncastrate metastasis was 13.5ng/ml and the median PSA doubling time was 3.4 months. At the diagnosis of metastasis, bone, lymph node and viscera were involved in 63%, 36%, and 6% of patients, respectively. Bone only metastases were found at initial metastatic diagnosis in 56 of 95 men (59%). Node-only metastases were identified in 30 patients (32%). The 3- and 5-year of cancer-specific survival from diagnosis of noncastrate metastases were 84% and 68%, respectively. In multivariate analysis, disease extent and PSA doubling time were significantly associated with survival outcome.

The 3- and 5-year actuarial disease-specific survival probabilities were 89% and 78% for a PSA doubling time of >3months and 71% and 42% for a PSA doubling time of <3 months, respectively. Only 26% of patients with extensive disease and a PSA doubling time of <3 months were alive 5 years after being diagnosed with noncastrate metastases, compared to 83% alive at 5 years who had minimal metastatic disease and a PSA doubling time of >3 months.

These data suggest that the risk of dying form prostate cancer is best determined from the initial pattern of metastatic spread and PSA kinetic, rather than time elapsing from prior disease states.

YossepowitchВ O, BiancoВ Jr.В FJ, EggenerВ SE, EasthamВ JA, ScherВ HI, ScardinoВ PT, GraefenВ M, LujГЎnВ M
Eur Urol 2006;epub
doi:10.1016/j.eururo.2006.10.045

Reviewed by UroToday.com Contributing Editor Christopher P. Evans, M.D.

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Radiation Therapy Combo Cures Prostate Cancer Long-Term

2007-04-16T11:25:00.001-07:00

Seventy-four percent of men treated with a combination of radiation seed implants and external beam radiation therapy for prostate cancer are cured of their disease 15 years following their treatment, according to a study released today in the International Journal of Radiation Oncology Biology Physics, the official journal of ASTRO.

This study was conducted by the physicians at the Seattle Prostate Institute. Doctors wanted to look at the combination of seed implants and external beam radiation therapy, two different types of radiation therapy, to prolong the long-term disease cure rates for prostate cancer. Over the course of 15 years, doctors followed 232 men with early-stage prostate cancer who received a course of external beam radiation therapy followed by permanent seed implants a few weeks later. Sixty-five percent of these patients had T2b-T3 disease and the entire group had an average pre-treatment PSA of 15 ng/ml.

Seed implants, also called brachytherapy, are small radioactive pellets, each about the size of a grain of rice. The seeds are inserted into the prostate through small needles during a brief outpatient procedure. External beam radiation therapy involves a series of 25 short daily outpatient treatments, where a radiation oncologist precisely directs high energy radiation beams to kill cancer cells. "This study is exciting because it shows that the combination of brachytherapy and external beam therapy are successful long-term at curing men of their prostate cancer," said John E. Sylvester, M.D., lead author of the study and the Director of the Seattle Prostate Institute in Seattle. "This is good news for men with prostate cancer since radiation therapy is less invasive, spares healthy tissue and helps patients return to regular activities sooner than surgery."

For more information about prostate cancer treatment options, please visit http://www.rtanswers.org.

ASTRO is the largest radiation oncology society in the world, with more than 8,500 members who specialize in treating patients with radiation therapies. As the leading organization in radiation oncology, biology and physics, the Society is dedicated to the advancement of the practice of radiation oncology by promoting excellence in patient care, providing opportunities for educational and professional development, promoting research and disseminating research results and representing radiation oncology in a rapidly evolving socioeconomic healthcare environment.

American Society for Therapeutic Radiology and Oncology (ASTRO)
8280 Willow Oaks Corporate Dr., Ste 500
Fairfax, VA 22031
United States
http://www.astro.org/

Speeding Development Of Novel Tracer For Prostate Cancer

2007-04-16T11:13:00.001-07:00

The collaborative work being performed by professionals across medical disciplines in the promising area of molecular imaging - from research scientists to nuclear medicine physicians, urologists, radiochemists and even veterinarians - provides encouraging news in fighting prostate cancer. This type of progressive - or translational - research can be seen in two papers published in the January issue of the Journal of Nuclear Medicine.

Researchers at Emory University in Atlanta, Ga., and at Nihon Medi-PhysicsвЂ™ research center in Chiba, Japan, collaborated closely in examining the potential of using the radiotracer FACBC to better stage or determine prostate cancer spread, said David M. Schuster, an assistant professor and director of the division of nuclear medicine and molecular imaging in EmoryвЂ™s radiology department. "Our two studies show the progression of molecular imaging in what is called translational research, the process of taking research and finding useful applications for it with patients," added co-author of "Initial Experience With the Radiotracer Anti 1-Amino-3-[18F]Fluorocyclobutane-1-Carboxylic Acid (Anti-[18F]FACBC) With PET/CT in Prostate Carcinoma." Together with "A Preliminary Study of Anti 1-Amino-3-[18F] Fluorocyclobutyl-1-Carboxylic Acid for the Detection of Prostate Cancer," the two papers illustrate the development of a promising radioisotope tracer (a radioactive substance) from in vitro stage (in a test tube) to in vivo (within a live subject) in animals to in vivo in individuals with prostate cancer, explained Schuster. The Emory pilot study with FACBC, performed with only 15 patients, shows that the amino acid analog may hold the potential to provide information to better stage or determine prostate cancer spread, said Schuster. He stressed that FACBC is not available for use with patients, and additional research needs to be done with larger groups of patients.

Other than skin cancer, prostate cancer is the most common type of cancer found in American men. Estimates show that there were more than 230,000 new cases of prostate cancer in this country last year. SchusterвЂ™s study is one of many in which researchers are exploring new and "better" radiotracers that could improve a physicianвЂ™s ability to stage cancer, for example, by providing higher sensitivity. This is very important since treatment and recovery outlook are dependent on the stage of cancer, said Schuster. "FACBC could eventually provide additional anatomical information about cancer location," he added, indicating that there could also be many "spin-off applications" for the tracer (for example, in patients with brain, breast and lung cancers). "This type of research is not a revolution, rather itвЂ™s an evolution; however, these kinds of evolutions can possibly lead to a revolution," explained Schuster, who is also seeking additional funding for this research.

The two studies used FACBC with positron emission tomography (PET) and PET with computed tomography (PET/CT), both standard imaging tools that can be used to pinpoint diseases in the body. When PET is used to image cancer, a radiotracer is injected into a patient, and it is drawn in higher concentrations to cancerous areas. The highly sensitive PET scan picks up the metabolic signal of actively growing cancer cells. The CT scan generates a detailed picture of internal anatomy, locating and revealing the size and shape of abnormal cancer growths. When these two results are fused together, the functional data from the PET imaging are correlated with anatomy on the CT images to provide a single detailed and informative image.

Tracers - such as 18F-FDG, 11C-choline, 11C-acetate and others - are currently used for diagnosing prostate cancer, said Shuntaro Oka, veterinarian and an assistant research associate at Nihon Medi-Physics. In OkaвЂ™s in vitro and in vivo study, FACBC had a high accumulation in cancer cells, small excretion into the bladder and a low accumulation in areas of inflammation, indicating that it could possibly "overcome drawbacks of some traditional PET tracers," he noted. "It is not unusual that the results of experiments lose touch with the results of clinical study; however, this time, the results of our basic studies correlated well with Dr. SchusterвЂ™s findings in patients with prostate cancer," said Oka. "This is good news for development of our compounds," he added, indicating clinical PET is not generally accepted in Japan; he hoped that FACBC could become "an agent to enhance the health and quality of life of patients."

Oka said the two research studies were definite examples of molecular imaging, a technique to visualize the activity of molecules in the body. PET showed the activity of amino acid transporters that "mediate" FACBC, the radiotracer that was developed in Mark M. GoodmanвЂ™s lab at Emory University, into prostate cancer. " вЂHot spotsвЂ™ on FACBC PET indicate the location of the amino acid transporters in target tissue and the siteвЂ™s increased activity of the amino acid transporters," said Oka. Schuster indicated that the research was conducted with individuals representing "a panoply of clinical knowledge" from Emory Healthcare and Winship Cancer Institute of Emory University, Emory University, the Atlanta VA Hospital and Nihon.

The American and Japanese collaborative research appears in the January issue of the Journal of Nuclear Medicine, which is published by SNM, the largest molecular imaging and nuclear medicine association. Authors of "Initial Experience With the Radiotracer Anti 1-Amino-3-[18F]Fluorocyclobutane-1-Carboxylic Acid (Anti-[18F]FACBC) With PET/CT in Prostate Carcinoma" are David M Schuster, John R Votaw, Weiping Yu, Jonathon A Nye and Mark M. Goodman, Radiology Department, Division of Nuclear Medicine; Peter T Nieh, Viraj Master and Muta M. Issa, Urology Department; and F. DuBois Bowman, Biostatistics Department, all at Emory University in Atlanta, Ga.

"A Preliminary Study of Anti 1-Amino-3-[18F]Fluorocyclobutyl-1-Carboxylic Acid for the Detection of Prostate Cancer" was written by Shuntaro Oka, Ryota Hattori, Fumie Kurosaki, Masahito Toyama, Yasunori Yoshida and Osamu Ito, all with the Research Center, Nihon Medi-Physics Co. Ltd., in Sodegaura, Chiba, Japan; and Larry A. Williams, Weiping Yu, John R. Votaw and Mark M. Goodman, all with the PET Center and the Radiology Department at Emory University, in Atlanta, Ga.

About SNM - Advancing Molecular Imaging and Therapy

SNM is an international scientific and professional organization of more than 16,000 members dedicated to promoting the science, technology and practical applications of molecular and nuclear imaging to diagnose, manage and treat diseases in women, men and children. Founded more than 50 years ago, SNM continues to provide essential resources for health care practitioners and patients; publish the most prominent peer-reviewed journal in the field (the Journal of Nuclear Medicine); host the premier annual meeting for medical imaging; sponsor research grants, fellowships and awards; and train physicians, technologists, scientists, physicists, chemists and radiopharmacists in state-of-the-art imaging procedures and advances. SNM members have introduced - and continue to explore - biological and technological innovations in medicine that noninvasively investigate the molecular basis of diseases, benefiting countless generations of patients. SNM is based in Reston, Va.; additional information can be found online at http://www.snm.org/.

Contact: Maryann Verrillo
Society of Nuclear Medicine

Metastatic Disease Of Screen-Detected Prostate Cancer

2007-04-16T10:35:00.001-07:00

UroToday.com- The number of men diagnosed with prostate cancer (CaP) per prostate cancer death (the incidence/mortality ratio) has increased due to either screening effort or improvements in treatment modalities. Due to a developing burden of overdiagnosis and treatment of CaP, a need for risk stratification of CaP patients exists. In the online edition of Cancer, the group of Dr. Fritz Schroeder, report on the prognostic factors related to the development of metastases in men with screen-detected CaP which is non-metastatic at diagnosis.

The European Randomized study of Screening for Prostate Cancer (ERSCP), Rotterdam database was used for this analysis. From 1993 to 1999 in Rotterdam 42,376 men were randomized between the screening and control arms. A cohort of 633 men diagnosed with non-metastatic CaP during their first screening visit in the first 4 years of ERSPC was identified. The primary endpoint for the analysis was the occurrence of metastatic disease and the secondary endpoint was overall survival.

Mean and median follow-up times for the 633 men were 7.1 and 7.5 years, respectively during which 41 men (6.5%) were diagnosed with metastatic disease. The 10-year metastatic-free survival was 90%. The mean time period from diagnosis until metastatic disease was 62 months. After 10 years the overall survival was 65%. A total of 232 men elected surgery and 5 (2.2%) developed metastatic disease.

In a multivariate regression model, the time to failure in surgery patients was significantly related to the initial PSA level (higher was worse). In the 334 men treated with radiotherapy, the group with a Gleason score >8 and, jointly a higher total number of biopsy cores positive for cancer showed a different failure pattern when compared to the rest of the radiotherapy patients. These patients had earlier time to metastases.

The data suggest that the predictive potential of the total number of biopsy cores with CaP and the biopsy Gleason score strongly affects the time to metastases during the first 60 months of the follow-up, but the initial PSA level and poorly differentiated tumors are the only predictors for metastases occurring after 60 months.

While the development of metastases is not common in men with screen-detected CaP, individual risk factors can help to predict for metastatic recurrence.

Stijn Roemeling, Ries Kranse, AndrГ© N. Vis, Claartje Gosselaar, Theo H. van der Kwast, Fritz H. SchrГ¶der
Cancer: VolumeВ 107, IssueВ 12, Date:В 15 December 2006, Pages:В 2779-2785

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A Meta-Analysis Of Diabetes Mellitus And The Risk Of Prostate Cancer

2007-04-16T10:20:00.001-07:00

UroToday.com- In 2004 a meta-analysis reported that patients with diabetes mellitus (DM) had a statistically significant decrease in risk (9%) of developing prostate cancer (CaP). This has now been validated in a larger meta-analysis reported by Drs. Kasper and Giovannunucci from Harvard Medical School. Their report appears in the November 2006 issue of Cancer Epidemiology Biomarkers and Prevention.

The goal of the new meta-analysis was to increase the number of articles included in the analysis from 14 to 19 and thereby the number of cases from 9,000 to >20,000 for enhanced statistical analysis. The authors also sought to determine if differences existed in patients in the pre-PSA compared to PSA era. The selection of published studies identified 325 articles of which 19 were chosen for extraction and analysis. While most publications did not specify whether patients had type I or type II DM, the age of participants suggested that most had type II DM. A variety of subset analyses were performed to address particular questions.

To determine the amount of heterogeneity that existed between the 19 studies a Cochran's Q test was performed. Then using a random-effects model, the authors found that DM was associated with a lower risk for CaP (RR, 0.84). Both cohort and case-control studies demonstrated heterogeneity. When analyzed by publication year, less heterogeneity existed as a group for the studies published prior to 2002 or after 2002 compared to all the studies combined.

To determine any difference in risk in the pre- and post-PSA eras, another subgroup analysis was done. The RR for pre-PSA was 0.94 and the RR for PSA era was 0.73. Separating studies that corrected for BMI from those that did not correct for BMI showed RRs of 0.82 and 0.87, respectively. Overall, the study showed that diabetic men have a statistically significant 16% decreased risk of developing CAP. The authors cite several possible explanations. DM and CaP may share additional factors that affect the risk of both diseases independently. This could include decreased insulin and IGF-I levels, or decreased testosterone levels.

This larger, robust meta-analysis strongly validates that men with DM are at decreased risk for development of CaP.

Jocelyn S. Kasper and Edward Giovannucci
Cancer Epidemiol Biomarkers Prev 2006 15: 2056-2062.

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Impact Of Surgical Margin Status On Long-Term Cancer Control After Radical Prostatectomy

2007-04-16T09:25:00.001-07:00

UroToday.com- Patterns of prostate cancer (CaP) recurrence following radical prostatectomy (RP) demonstrate that up to 50% of patients will develop a high PSA level by 10 years after RP with most occurring within the first two years, but 20% occurring at greater than 5 years. Surgical margin status may impact this and is related to surgical technique, argues Dr. Orvieto from the University of Chicago who reports on the surgical series of Dr. Charles Brendler in the BJU International.

Between 1994 and 2004 a cohort of 996 men underwent RP by Dr. Brendler for clinically localized CaP. Mean patient age was 60 years and no patient received either neoadjuvant therapy or adjuvant therapy before biochemical failure. Pelvic lymph node dissection was performed in 44.5%. During pathologic review, any tumor at the inked margin was noted as a positive surgical margin (PSM), which was defined as focal if a solitary PSM and extensive when multifocal PSM was reported. Biochemical recurrence (BR) was defined as a PSA >0.1ng/ml and confirmed on a repeat assay.

Clinical stage was T1c in 60% and T2 disease in 40%. Ninety percent of patients had Gleason score 5-7 tumors on biopsy. Overall, a PSM was identified in 88 of 996 cases (8.8%). Only 12 of 694 patients with organ-confined disease (1.7) had a PSM. In those with extra-capsular extension, 60 of 241 (24.9%) and 16 of 59 (27%) with pT3a and pT3b disease had a PSM, respectively. Both clinical stage and pathological stage were statistically correlated with incidence of a PSM. Higher post-operative Gleason score did not correlate. The authors state that surgical modifications in 1995 and 2000 were followed by a significant decrease in PSM rates over time in patients with extra-capsular extension.

Overall, 97% of the cohort was available for follow-up at a mean of 6.4 years, during which 98 patients (10.1%) developed BR. Of these, 37% experienced a BR within a year of surgery and 61% with the first 2 years. Only 12% had a BR after 5 years from RP. The mean time to BR was 2.4 years. Follow-up was available in 871 men (90%) at 5 years and 135 men (14%) at 10 years. Kaplan-Meier analysis showed 5- and 10-year biochemical disease free survival rates of 90% and 86%, respectively. Adjuvant therapy was given to 89 men (9.2%) after RP. Nine men died from CaP.

Biochemical progression developed in 69 of 883 patients (8%) with negative surgical margins compared to 29 of 85 men (34%) with a PSM. Ten-year biochemical disease-free survival estimates for negative and positive surgical margins were 90% and 60%, respectively. A PSM was a significant predictor of recurrence in patients with both organ confined and pT3a disease. However, the risk of BR in those with pT3b disease was not impacted by the presence of a PSM. On multivariate analysis, the presence of a PSM and final pathological stage and Gleason score were the strongest predictors of subsequent BR.

Marcelo A. Orvieto, Nejd F. Alsikafi, Arieh L. Shalhav, Brett A. Laven, Gary D. Steinberg, Gregory P. Zagaja, Charles B. Brendler
BJU InternationalВ 98В (6),В 1199-1203.
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Risk Of Dying From Prostate Cancer Increased By Excess Weight And Adult Weight Gain

2007-04-16T09:12:00.001-07:00

A new study finds that obesity increases the risk of death from prostate cancer, even though it does not increase the overall risk a man will be diagnosed with the disease. Published in the February 15, 2007 issue of CANCER, a peer-reviewed journal of the American Cancer Society, the study reveals that higher body mass index (BMI) and weight gain in adulthood correlated strongly with increased risk of death from prostate cancer. However, no such association was found between BMI or weight gain and the development of the cancer. The study is the first large, prospective study to identify increasing weight after age 18 as an independent, poor prognostic factor for prostate cancer.

The incidence of obesity has increased dramatically worldwide. In the U.S., for example, the number of states reporting obesity rates greater than 20 percent increased from zero in 1985 to 46 in 2005. Today, 30 percent of American adults are categorized as obese - i.e., a BMI greater than 30. Obesity is linked to chronic medical problems, including heart disease, diabetes, gallbladder disease, and stroke. In addition, studies indicate higher BMIs are linked to some cancers, including breast and colorectal cancer.

The influence of obesity and weight gain on the development of localized and aggressive forms of prostate cancer is not clear. A recent meta-analysis suggested only a weak correlation between obesity and prostate cancer incidence. However, clinical studies have suggested that men with higher BMI or men who gained weight most rapidly since age 25 were at greater risk of treatment failure or being diagnosed with advanced disease.

Led by Margaret E. Wright, Ph.D., of the Division of Cancer Epidemiology and Genetics at the National Cancer Institute in Bethesda, MD, researchers followed 287,760 men, ages 50-71 years as part of the NIH-AARP Diet and Health Study to examine the individual impact of BMI and adult weight change on the incidence, severity and outcome of prostate cancer.

The researchers found that higher BMI and weight gain since the age of 18 were associated with significantly higher risk of death from prostate cancer. As BMI increased, so did the relative risk of death. Men who were overweight (BMI 25-29.9) had a 25 percent higher risk, mildly obese men (BMI 30-34.9) had a 46 percent higher risk, and severely obese men (BMI greater than 35) had a 100 percent, or doubled risk. Similarly, men who gained weight since the age of 18 were also at increased risk of a fatal outcome. Neither overweight nor obesity, however, was associated with developing prostate cancer.

That obesity did not impact the incidence of prostate cancer is consistent with findings from most other studies. However, that "BMI and adult weight gain were each linked with higher prostate cancer mortality," significantly links "adiposity to prostate cancer progression leading to death," conclude the authors.

###

Article: "Prospective Study of Adiposity and Weight Change in Relation to Prostate Cancer Incidence and Mortality," Margaret E. Wright, Shih-Chen Chang, Arthur Schatzkin, Demetrius Albanes, Victor Kipnis, Traci Mouw, Paul Hurwitz, Albert Hollenbeck, Michael F. Leitzmann, CANCER; Published Online: January 15, 2007 (DOI: 10.1002/cncr.22443); Print Issue Date: February 15, 2007.

Contact: David Greenberg
John Wiley & Sons, Inc.

The Prognostic Significance Of Perineural Invasion In Prostatic Cancer Biopsies

2007-04-16T08:20:00.001-07:00

UroToday.com- Whether perineural invasion (PNI) identified in prostate cancer (CaP) biopsies is associated with disease recurrence is unclear from the literature. In an attempt to resolve this uncertainty, a systematic review was performed by Dr. Patricia Hamden and colleagues in the UK and published in the online edition of Cancer. What they found was that variable study design, execution and reporting excluded a definitive meta-analysis, but evidence suggests that PNI in biopsies was a significant prognostic indicator.

The authors' strategy used 128 search terms to identify articles published between 1990 and 2005. A total of 41,295 titles were reviewed by at least 2 reviewers and 128 articles identified for close evaluation. Ultimately, 10 surgical and 11 radiotherapy articles on PNI in biopsies as it related to patient outcomes were used in the report. Data items specific to biopsy PNI in CaP included biopsy procedure (amount of cores, number of nerves present and identification of PNI), histological slide preparation and pathological interpretation (consistency of identification, inclusion of information if no nerves were present).

No study reported on all data items and incomplete items ranged from 18% to 61% with a median of 39%. Exclusion criteria were variable, but included a history of prior treatment, unavailability of biopsies for review or the failure to obtain at least 4 biopsies. Only 1 surgical and 1 radiotherapy article was prospective. In surgical patients details on nerve sparing was generally lacking. In 12 studies, biopsies were reviewed for the presence of PNI and in 1 study 60% of biopsies were reviewed for this. In 5 studies the slides were not reviewed but the diagnosis was taken from the original report and in 3 articles the information was not provided. Only 2 articles reported blinded pathologic review. Individual patient data was sufficient in 5 articles to permit reanalysis.

The proportion of patients with PNI varied between 7% and 12% (median 9%) when the diagnosis was obtained form the original report and between 7% and 43% (median 23%) when slides were reviewed to identify PNI. Most studies had short (<6 months) of clinical follow-up. Overall, 6 of 10 surgical and 5 of 11 radiotherapy studies identified PNI as a prognostic factor in univariate analysis. Surgical articles that included a larger number of patients with less patient exclusion reported that PNI was independently prognostic in multivariate analysis with PSA and biopsy Gleason score. More than two-thirds of external radiotherapy studies but no brachytherapy study showed prognostic significance for perineural invasion. The highest incidence of PNI was found in locally-advanced disease.

Surprising to the authors were that none of the articles considered that the presence of nerves in the biopsies was a prerequisite for patient inclusion and no article provided data on the reproducibility of the PNI diagnosis. The authors conclude that the importance of PNI was likely to have been underestimated by the inclusion of uninformative test results (biopsies with no nerves in the specimens) and that despite this, the majority of studies including those performing multivariate analysis found prognostic significance to PNI. The weight of evidence supports PNI as of prognostic significance.

Patricia Harnden, Michael D. Shelley, Hayley Clements, Bernadette Coles, R. Sandy Tyndale-Biscoe, Brian Naylor, Malcolm D. Mason

Cancer 2006
Published Online: 22 Nov 2006
вЂЁDOI: 10.1002/cncr.22388

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Novel Regulation Of The Common Tumor Suppressor PTEN

2007-04-16T08:10:00.000-07:00

PTEN is one of the most commonly mutated tumor suppressor genes. It is an antagonist for many cellular growth, proliferation and survival processes. When mutated or deleted, it causes cancers of the prostate, breast, colon, and brain. Researchers led by scientists at Memorial Sloan-Kettering Cancer Center have now identified fundamentally novel regulatory mechanisms of PTEN function. The findings from two related studies are published in the January 12 issue of Cell.

The first is research by Dr. Xuejen Jiang's laboratory at Sloan-Kettering which identified a novel component that regulates PTEN. This protein, NEDD4-1, controls protein stability in cells. Researchers found that NEDD4-1 is a key component in eliminating PTEN from cells by adding a molecular tag, ubiquitin, to PTEN causing degradation in the cellular machinery called proteasome. In a mouse model for prostate cancer, the researchers found that areas with aggressive tumor contained low PTEN levels and high NEDD4-1. They concluded that NEDD4-1 could promote cancer development by down-regulating PTEN.

The second study by Dr. Pier Paolo Pandolfi of Memorial Sloan-Kettering and colleagues found that the ubiquitination of PTEN by NEDD4-1 also regulates another important aspect of PTEN, its cellular localization.

PTEN has been found mostly in the cytoplasm but has been known to also be in cell nuclei. While the cytoplasmic function of PTEN is now quite well understood, its nuclear functions have been elusive. Looking at a family with an inherited PTEN mutation that caused them to have the cancer-susceptibility condition, Cowden Syndrome, researchers found that the patients' colon cancer strikingly lacked nuclear PTEN.

The Pandolfi and Jiang labs showed that the PTEN mutation in these patients prevented the addition of ubiquitin by NEDD4-1, providing a molecular mechanism for the detrimental effect of the mutant PTEN protein. They showed that the single ubiquitin tagging is necessary to import PTEN into the cell nucleus where it is protected from degradation and cancer is initiated.

According to the researchers, the uncovered key role of PTEN degradation provides a new therapeutic strategy. Since ubiquitination has both positive (single tag) and negative (repetitive tagging) effects, a class of drugs, the proteasome inhibitors, that selectively blocks the degrading effects of ubiquitination, should now be studied as possible treatments for cancers with PTEN mutations.

###

The research was supported by grants from The National Institutes of Health and the American Cancer Society.

Contact: Joanne Nicholas
Memorial Sloan-Kettering Cancer Center

Call For Better Prostate Cancer Biopsies

2007-04-16T07:12:00.001-07:00

Routine collection of additional information from prostate cancer biopsies could allow better decisions about the best choice of treatment, according to a study published in the journal Cancer*.

Through a systematic review of the published evidence, scientists funded by the NHS Cancer Screening Programme, Cancer Research UK and Cancer Research Wales found evidence of a link between the spread of cancer to nerves in the prostate gland - called 'perineural invasion' or PNI - and a poorer outlook for prostate cancer patients.

The clinical significance of PNI has been unclear, and therefore current guidelines for pathologists make no mention of PNI, leaving it up to individual doctors to decide whether they check for it or not.

This review shows a significant association between PNI and the risk of disease recurrence but the risk associated with PNI remains impossible to fully quantify from the few studies that have been done so far. The researchers are recommending to the Royal College of Pathologists that PNI should be assessed in every case of prostate cancer. This would help determine more precisely the size of the associated risk and so aid future decisions about treatment.

Prostate cancer is the most common cancer in men, with more than 32,000 cases diagnosed each year in the UK, but the best approach to treatment is not always clear. Doctors currently have very little evidence to rely on when deciding on the most appropriate treatment option.

Widespread use in the US of the PSA (Prostate-Specific Antigen) test to identify asymptomatic prostate cancer has led to an increase in the number of prostate tumours detected, but the PSA test gives only limited information regarding a patient's prognosis.

The best management of early diagnosed tumours is particularly hard to judge. Options include radical prostatectomy - surgical removal of the prostate - and active surveillance or so-called 'watchful waiting', which may be chosen on the basis that most prostate tumours are slow-growing and occur in elderly men in whom prostate cancer will not be their cause of death. If, however, the cancer turns out to be growing faster, then active treatment is offered.

Cancer Research UK's Dr Patricia Harnden, lead author of the report, said: "We've shown that PNI increases the risk of recurrence in prostate cancer. If it is found in a prostate biopsy, it could mean the difference between choosing 'watchful waiting' and immediately treating the cancer, or perhaps giving a longer course of therapy. Pathology is not being used to its full potential in prostate cancer if PNI is not looked for.

" Making PNI a mandatory reporting item in the guidelines of the Royal College of Pathologists would have two effects - it would help gather more data on the exact association between PNI and risk of recurrence, and it would enable doctors to make more informed decisions on how best to treat their patients. We must also ensure that future studies of pathological prognostic factors such as PNI are designed well enough to properly assess their significance."

Julietta Patnick, director of NHS Cancer Screening Programmes, said: "I am very pleased that the NHS Cancer Screening Programmes has been able to facilitate this significant work. The results of this review will assist health professionals in making the best treatment decisions for patients."

Professor John Toy, medical director of Cancer Research UK, said: "Some prostate cancer patients have normal PSA levels, and some healthy men have high PSA levels that are not caused by cancer. It can often be extremely difficult to predict with certainty the prognosis for many men with early prostate cancer.

"Therefore, the identification of a prognostic marker that indicates an aggressive cancer would be of great value. PNI in a prostate biopsy may be such a marker. We must ensure that no opportunity to gather potentially important information about prostate cancer is wasted."

Professor Adrian Newland, president of the Royal College of Pathologists, said: "The Royal College of Pathologists welcomes this systematic review of PNI in prostatic cancer biopsies, particularly the identification of PNI as a reliable predictor of adverse clinical outcome.

"Detailed histological evaluation by medically-trained histopathologists is essential in the assessment of cancer specimens, particularly the identification of features of clinical value to patients and their supervising clinicians alike. The Royal College of Pathologists endorses the view expressed in the paper that well designed studies using pre-defined stringent protocols are now required to provide robust objective estimates of risk, following identification of PNI in prostatic core biopsies, as an aid in the planning of treatment for men diagnosed with prostate cancer."

* Harnden et al. (2007) "The prognostic significance of perineural invasion in prostatic cancer biopsies: A systematic review" CANCER; Vol. 109 Issue 1, pp13-24

For more statistics on prostate cancer, please visit Cancer Research UK's CancerStats website.

The NHS Prostate Cancer Risk Management programme

-- Information on Prostate Cancer Risk Management, prostate cancer and the PSA test is available here.

-- For more information about the NHS Cancer Screening Programmes, contact Andrea Whitfield, Caroline Greenaway, Sarah Gibbs or Helen Ketton in the press office on 020 7025 7510 or email screening@westminster.com

About Cancer Research UK

Together with its partners and supporters, Cancer Research UK's vision is to beat cancer.

-- Cancer Research UK carries out world-class research to improve understanding of the disease and find out how to prevent, diagnose and treat different kinds of cancer.

-- Cancer Research UK ensures that its findings are used to improve the lives of all cancer patients.

-- Cancer Research UK helps people to understand cancer, the progress that is being made and the choices each person can make.

-- Cancer Research UK works in partnership with others to achieve the greatest impact in the global fight against cancer.

http://www.cancerresearchuk.org

Watson Announces Positive Phase 3 Study Results On Silodosin For Treatment Of Benign Prostatic Hyperplasia

2007-04-16T07:07:00.001-07:00

Watson Pharmaceuticals, Inc. (NYSE: WPI), a leading specialty pharmaceutical company, today announced positive top-line data from two Phase 3 studies of silodosin, the Company's investigational drug being studied for the treatment of signs and symptoms of benign prostatic hyperplasia (BPH).

The primary objective of the trials was to demonstrate that 8mg silodosin given once daily for 12 weeks was superior to placebo for the relief of BPH symptoms, including both obstructive and irritative symptoms, as measured by a baseline-to-endpoint change in the total score of the International Prostate Symptom Score-1 (IPSS-1). Secondary endpoints included improvements in maximum urine flow (Qmax). Very rapid and statistically significant improvements were seen in both of these endpoints.

Silodosin was well tolerated in both studies. Cardiovascular and blood pressure related side effects, including dizziness and orthostasis, were low in both trials. As expected with highly uroselective alpha blockers, ejaculations with little or no semen were the most commonly reported side effect seen in the trials. The vast majority of these reports were mild to moderate in intensity and patient withdrawal from the trial was low.

Results from these studies will be submitted for presentation at a medical meeting at a later date.

"We are extremely encouraged with the efficacy that was demonstrated in these trials, supporting the potential clinical utility of silodosin in treating BPH," said Dr. Charles Ebert, Watson's Senior Vice President, Research and Development. "Our ongoing one year safety study remains on track to be completed this fall and we expect to submit a New Drug Application to FDA in the first half of 2008."

"The completion of the silodosin Phase 3 studies is an important milestone for Watson," continued Dr. Ebert. "As BPH is one of the most commonly treated disorders by urologists, silodosin is expected to greatly enhance our growing urology franchise."

Benign Prostatic Hyperplasia (BPH)

BPH is characterized by a non-cancerous enlarged prostate that leads to obstructive and irritative urinary symptoms. In the United States (US) BPH affects more than half of men in their sixties and as many as 90 percent of men by the age of 85. Additionally, approximately $1.7 billion is spent annually on BPH prescription drug treatment.

Silodosin

Silodosin is a novel, highly uroselective alpha (1A)-adrenoceptor antagonist originally developed by Kissei Pharmaceutical Co., Ltd. in Japan and licensed to Watson for the US, Canada and Mexico markets. Silodosin preferentially binds to the alpha (1A) receptors in the prostate and bladder neck relative to cardiovascular associated receptors, thereby maximizing target organ activity while minimizing the potential for blood pressure effects. Urief(R) (silodosin) 4mg, dosed twice daily, was launched in Japan in May 2006 and is marketed in cooperation with Daiichi Pharmaceutical Co., Ltd.

About Watson Pharmaceuticals, Inc.

Watson Pharmaceuticals, Inc., headquartered in Corona, California, is a leading specialty pharmaceutical company that develops, manufactures, markets, sells and distributes brand and generic pharmaceutical products. Watson pursues a growth strategy combining internal product development, strategic alliances and collaborations and synergistic acquisitions of products and businesses.

For press releases and other company information, visit Watson Pharmaceuticals' Web site at http://www.watsonpharm.com.

About Kissei Pharmaceutical Co., Ltd.

Kissei Pharmaceutical Co., Ltd., headquartered in Matsumoto, Nagano prefecture, founded in 1946, is a Japanese pharmaceutical company that develops, manufactures, markets, sells and distributes brand pharmaceutical products. Kissei is primarily focused on three important fields of new drug research: urogenital, endocrinology & metabolism and immunology & allergy.

Forward-Looking Statement

Any statements contained in this press release that refer to future events or other non-historical facts are forward-looking statements that reflect Watson's current perspective of existing trends and information as of the date of this release. Except as expressly required by law, Watson disclaims any intent or obligation to update these forward-looking statements. Actual results may differ materially from Watson's current expectations depending upon a number of factors affecting Watson's business. These factors include, among others, the difficulty of predicting the timing or outcome of clinical studies, product development efforts and FDA or other regulatory agency approvals or actions; whether the results of clinical trials for silodosin and other information will be sufficient to support approval of silodosin by FDA and other regulatory authorities; delays regarding the regulatory approval process, including the timing and scope of approval received, if any; market acceptance and continued demand for Watson's products, including silodosin, if approved; patents and other intellectual property rights held by competitors and other third parties; successful compliance with FDA and other governmental regulations applicable to Watson's products and/or business; and such other risks and uncertainties detailed in Watson's periodic public filings with the Securities and Exchange Commission, including but not limited to Watson's Annual Report on Form 10-K for the year ended December 31, 2005 and its Quarterly Report on Form 10-Q for the quarter ended September 30, 2006.

Watson Pharmaceuticals, Inc.
http://www.watsonpharm.com

Dendreon's PROVENGE Granted FDA Priority Review For The Treatment Of Asymptomatic, Metastatic, Androgen-Independent Prostate Cancer

2007-04-16T06:21:00.001-07:00

Dendreon Corporation (Nasdaq: DNDN) today announced that the U.S. Food and Drug Administration (FDA) has accepted for filing and has assigned priority review status to the Company's Biologics License Application (BLA) for PROVENGE(R) (sipuleucel-T), its investigational active cellular immunotherapy for the treatment of asymptomatic, metastatic, androgen-independent (also known as hormone refractory) prostate cancer.

Priority Review is granted to products that, if approved, would provide a significant improvement in the safety or effectiveness of the treatment, diagnosis or prevention of a serious or life-threatening disease. The goal for reviewing a product with Priority Review status is six months from the filing date. The Prescription Drug User Fee Act (PDUFA) date for completion of review by the FDA of the PROVENGE BLA is May 15, 2007.

"Clinical trials have shown that PROVENGE increases survival and is generally well tolerated in men with late-stage prostate cancer, a highly prevalent disease for which there are currently few available treatment options," said Mitchell H. Gold, president and chief executive officer of Dendreon. "We are extremely pleased the FDA has granted priority review to PROVENGE, which may represent an important new treatment option for men suffering from prostate cancer."

Prostate cancer is the most common non-skin cancer in the United States and the third most common cancer worldwide. More than one million men in the United States have prostate cancer, with an estimated 232,000 new cases of prostate cancer diagnosed each year. More than 30,000 men die each year of the disease.

The BLA submission is based primarily on an improvement in overall survival observed in Study D9901, a multi-center, randomized, double-blind, placebo-controlled Phase 3 Study, the results of which were published in the July issue of the Journal of Clinical Oncology.

About PROVENGE

PROVENGE (sipuleucel-T) is an investigational product that may represent the first in a new class of active cellular immunotherapies (ACIs) that are uniquely designed to stimulate a patient's own immune system. PROVENGE is in late-stage clinical development for the treatment of patients with advanced prostate cancer. In clinical studies, patients typically received three infusions over a one-month period as a complete course of therapy.

About Dendreon

Dendreon Corporation is a biotechnology company whose mission is to target cancer and transform lives through the discovery, development and commercialization of novel therapeutics that harness the immune system to fight cancer. The Company applies its expertise in antigen identification, engineering and cell processing to produce active cellular immunotherapy product candidates designed to stimulate an immune response. Active cellular immunotherapy holds promise because it may provide patients with a meaningful clinical benefit, such as survival, combined with low toxicity. The Company has headquarters in Seattle and is traded on the Nasdaq Global Market under the symbol DNDN. For more information about the Company and its programs, visit http://www.dendreon.com.

Except for historical information contained herein, this news release contains forward-looking statements that are subject to risks and uncertainties surrounding the efficacy of PROVENGE to treat men suffering from prostate cancer, risks and uncertainties surrounding the presentation of data to the FDA and approval of product applications by the FDA and risks and uncertainties inherent in the process of discovering, developing and commercializing drugs that are safe and effective for use as human therapeutics. Factors that may cause such differences include risks related to our limited operating history, risks associated with completing our clinical trials, the risk that the safety and/or efficacy results of a clinical trial for PROVENGE will not support an application for a biologics license, the risk that the FDA may interpret data differently than we do or require more data or a more rigorous analysis of data than expected, the risk that the FDA will not approve a product for which a biologics license has been applied, the risk that the results of a clinical trial for PROVENGE or other product may not be indicative of results obtained in a later clinical trial, risks that we may lack the financial resources and access to capital to fund required clinical trials or commercialization of PROVENGE, our dependence on the efforts of third parties, and our dependence on intellectual property. Further information on the factors and risks that could affect Dendreon's business, financial condition and results of operations are contained in Dendreon's public disclosure filings with the U.S. Securities and Exchange Commission, which are available at http://www.sec.gov.

Dendreon Corporation
http://www.dendreon.com

Tomato-Broccoli Combo Shown To Be Effective In Shrinking Prostate Tumours

2007-04-16T06:10:00.001-07:00

A new University of Illinois study shows that tomatoes and broccoli--two vegetables known for their cancer-fighting qualities--are better at shrinking prostate tumors when both are part of the daily diet than when they're eaten alone.

"When tomatoes and broccoli are eaten together, we see an additive effect. We think it's because different bioactive compounds in each food work on different anti-cancer pathways," said University of Illinois food science and human nutrition professor John Erdman.

In a study published in the January 15 issue of Cancer Research, Erdman and doctoral candidate Kirstie Canene-Adams fed a diet containing 10 percent tomato powder and 10 percent broccoli powder to laboratory rats that had been implanted with prostate cancer cells. The powders were made from whole foods so the effects of eating the entire vegetable could be compared with consuming individual parts of them as a nutritional supplement.

Other rats in the study received either tomato or broccoli powder alone; or a supplemental dose of lycopene, the red pigment in tomatoes thought to be the effective cancer-preventive agent in tomatoes; or finasteride, a drug prescribed for men with enlarged prostates. Another group of rats was castrated.

After 22 weeks, the tumors were weighed. The tomato/broccoli combo outperformed all other diets in shrinking prostate tumors. Biopsies of tumors were evaluated at The Ohio State University, confirming that tumor cells in the tomato/broccoli-fed rats were not proliferating as rapidly. The only treatment that approached the tomato/broccoli diet's level of effectiveness was castration, said Erdman.

"As nutritionists, it was very exciting to compare this drastic surgery to diet and see that tumor reduction was similar. Older men with slow-growing prostate cancer who have chosen watchful waiting over chemotherapy and radiation should seriously consider altering their diets to include more tomatoes and broccoli," said Canene-Adams.

How much tomato and broccoli should a 55-year-old man concerned about prostate health eat in order to receive these benefits? The scientists did some conversions.

"To get these effects, men should consume daily 1.4 cups of raw broccoli and 2.5 cups of fresh tomato, or 1 cup of tomato sauce, or ВЅ cup of tomato paste. I think it's very doable for a man to eat a cup and a half of broccoli per day or put broccoli on a pizza with ВЅ cup of tomato paste," said Canene-Adams.

Erdman said the study showed that eating whole foods is better than consuming their components. "It's better to eat tomatoes than to take a lycopene supplement," he said. "And cooked tomatoes may be better than raw tomatoes. Chopping and heating make the cancer-fighting constituents of tomatoes and broccoli more bioavailable."

"When tomatoes are cooked, for example, the water is removed and the healthful parts become more concentrated. That doesn't mean you should stay away from fresh produce. The lesson here, I think, is to eat a variety of fruits and vegetables prepared in a variety of ways," Canene-Adams added.

Another recent Erdman study shows that rats fed the tomato carotenoids phytofluene, lycopene, or a diet containing 10 percent tomato powder for four days had significantly reduced testosterone levels. "Most prostate cancer is hormone-sensitive, and reducing testosterone levels may be another way that eating tomatoes reduces prostate cancer growth," Erdman said.

Erdman said the tomato/broccoli study was a natural to be carried out at Illinois because of the pioneering work his colleague Elizabeth Jeffery has done on the cancer-fighting agents found in broccoli and other cruciferous vegetables. Jeffery has discovered sulfur compounds in broccoli that enhance certain enzymes in the human body, which then act to degrade carcinogens.

"For ten years, I've been learning how the phytochemicals in tomatoes affect the progression of prostate cancer. Meanwhile Dr. Jeffery has been investigating the ways in which the healthful effects of broccoli are produced. Teaming up to see how these vegetables worked together just made sense and certainly contributes to our knowledge about dietary treatments for prostate cancer," said Erdman.

###

Authors of the tomato/broccoli study are Kirstie Canene-Adams, Brian L. Lindshield, Elizabeth H. Jeffery, and John W. Erdman Jr. at the University of Illinois and Shihua Wang and Steven K. Clinton of The Ohio State University. The study was funded by the American Institute for Cancer Research and the U.S. Department of Agriculture.

The U of I study of the effects of tomato carotenoids on serum testosterone was published in the December 2006 issue of the Journal of Nutrition. Authors are Jessica K. Campbell, Chad K. Stroud, Manabu T. Nakamura, Mary Ann Lila, and John W. Erdman Jr. Funding was provided by the National Institutes of Health's National Cancer Institute.

Contact: Phyllis Picklesimer
University of Illinois at Urbana-Champaign

Prostate Cancer Detection And Screening Session I - AUA 2006

2007-04-16T03:41:00.001-07:00

UroToday.com - A Podium Session on Prostate Cancer Detection and Screening took place on Sunday May 21, 2006 at the annual AUA meeting in Atlanta. Some highlights from the 12 papers presented are as follows.

Dr. Ian Thompson, San Antonio, TX reported on ability for PSA to detect CaP in finasteride treated patients. Patients in the PCPT study who were on placebo or finasteride and underwent prostate biopsy were evaluated. Receiver operator characteristic curves (ROC) were calculated for the presence and absence of CaP and Gleason score. Of the 5,112 men in the placebo group, 1,111 were diagnosed with CaP compared to 695 of 4,579 men in the finasteride group. The area under the ROC curve was greater for finasteride than placebo. This was true for cancer detection overall and for high-grade disease. This study suggests a bias toward increased detection of CaP and high-grade CaP in men treated with finasteride in the PCPT study.

Dr. Loeb, Washington, DC stated that a PSA velocity (PSAV) of 0.5ng/ml/year should be used in men under age 60. Using the database of Dr. Catalona, 6,844 men under age 60 were identified and 346 of these were diagnosed with CaP. Analysis of their PSAV showed that a PSAV >0.5ng/ml/year was more predictive of CaP than age, total PSA, family history or race. Even those men with a PSA <0.25ng/ml had similar results. The sensitivity, specificity and positive and negative predictive values were 62%, 85%, 18%, and 98%, respectively.

Dr. Georg Bartsch, Innsbruck Austria and colleagues in several other countries presented an update on the Tyrolean CaP screening study. The program using PSA has been in place since 1993. Men diagnosed with CaP could go on to radical prostatectomy. Migration to lower stage of CaP and an increase in the number of organ-confined tumors was observed since the start of the program. A reduction in the mortality rates was observed in Tyrol and the rest of Austria (where PSA screening was not introduced). Dr. Bartsch concluded that the decline in death is likely a result of downstaging through surgical curable disease and successful treatment.

A presentation from Dr. Alschibaja, Munich Germany suggests that clinically insignificant CaP cannot be reliably predicted. A cohort of 349 patients undergoing radical prostatectomy had pathology specimens analyzed. Of these, 38 (9.2%) met the criteria for insignificant CaP. The model generated had a sensitivity of 84.2% and a specificity of 90.4%. The positive predictive value was only 51.5%, suggesting that 9.4% of clinically significant tumors would be missed.

By Christopher P. Evans, M.D.

UroToday - the only urology website with original content written by global urology key opinion leaders actively engaged in clinical practice.

To access the latest urology news releases from UroToday, go to:
http://www.urotoday.com

Copyright © 2006 - UroToday

Prostate Cancer Basic Research Session II - AUA 2006

2007-04-16T03:37:00.001-07:00

UroToday.com - A Discussed Poster Session on Prostate Cancer Basic Research took place on Sunday May 21, 2006 at the annual AUA meeting in Atlanta. A few of the many interesting posters on basic and potential translation science are described herein.

Dr. Davis Syme, Melbourne, Australia reported the effect of castration on cavernous nerve graft regeneration. Rats underwent bilateral cavernous nerve neurotomy followed by unilateral interpositional nerve graft using the genitofemoral nerve. Animals were then randomized to undergo castration, remain hormonally intact or receive testosterone. Electrostimulation of the nerve grafts was performed at 3 months and histologic analysis performed. Castration resulted in a significant reduction to electrostimulation and clinical application suggests that nerve grafts would be of little use in patients who may need androgen deprivation following surgery.

Dr. Christopher Evans, UC Davis presented work in a chimeric animal tumor model. His laboratory demonstrated that neuropeptide overexpressing androgen-insensitive CaP cells supported the growth and migration of androgen-sensitive CaP cells in androgen-deprived in vitro and in vivo environments. They have also shown that CaP cells express neuropeptides at the time of androgen-withdrawal. Taken together, this suggests that at the time of castration, some androgen-sensitive CaP cells may escape cell death due to paracrine support from surrounding neuropeptide expressing CaP cells.

Dr. Deka from Northwestern University reported that variants in the HEPSIN gene are associated with CaP in Caucasian men. The HEPSIN gene is located on chromosome 9q and codes for a transmembrane cell surface serine protease that is over-expressed in CaP. A comparison was made between 604 men with CaP and 576 controls, all Caucasian. Five of 11 single nucleotide polymorphisms on the HEPSIN gene were found to have significant differences in allele frequencies between the groups. This suggests an association between genetic variants in HEPSIN and CaP carcinogenesis in Caucasian men.

Dr. Wu from the laboratory of Dr. Dan Theodorescu, University of Virginia reported on the tumor suppressor gene PTEN and its effect on CaP cell migration in the bone microenvironment. PTEN was expressed in a PTEN-null CaP cell line, C4-2. The PTEN cells selectively migrated towards proteins expressed by bone calavaria compared to proteins expressed by lung fibroblast cells. Compared to control cells, the PTEN cells did not show increased proliferation, suggesting that the effect is purely on migration and not due to enhanced growth. Further experiments identified the PTEN mechanism as mediated through the small GTPase Rac1.

By Christopher P. Evans, M.D.

UroToday - the only urology website with original content written by global urology key opinion leaders actively engaged in clinical practice.

To access the latest urology news releases from UroToday, go to:
http://www.urotoday.com

Copyright © 2006 - UroToday

Prostate Cancer Basic Research Session I - AUA 2006

2007-04-16T02:54:00.001-07:00

UroToday.com - A Discussed Poster Session on Prostate Cancer Basic Research took place on Sunday May 21, 2006 at the annual AUA meeting in Atlanta. Many interesting posters on basic and potential translation science were presented. A few of these are described herein.

Dr. Stephen Freedland and colleagues, Baltimore MD compared gene expression patterns by microarray from obese and normal weight men. They found differences greater than expected by chance alone. 3-hydroxymethyl glutaryl coA, a rate limiting enzyme in ketone body production was significantly lower in obese men.

Dr. Eric Klein, Cleveland Clinic presented their work on a virus closely related to murine leukemia viruses that were identified in prostate tumors of men homozygous for the R462Q mutation in the HPC1 gene. This work suggests that there may be a link between viral infection and the development of CaP in men with a mutated gene.

A research group from Japan and California had their work on a biomarker in different ethnic cohorts presented by Dr. Enokida. They found that GSTP-1 gene hypermethylation was a biomarker for CaP in African-American as opposed to Caucasian or Asian men, but that it strongly influenced tumor progression in Asian men with CaP.

Dr. Ralf Herwig presented exciting work from Austrian collaborators regarding a new method to differentiate between benign and malignant prostate disease. To do this, they isolated peripheral blood mononuclear cells from 25 men with CaP and 10 healthy controls. Using cell surface antigens, the cells populations were separated by flow cytometry and intracellular PSA measured. Differentiation between malignant and benign disease was achieved using the CD14/PSA staining. PSA was only found in activated CD14 cells, and was much higher in metastatic compared to localized CaP.

Dr. Mark Rubin's group from Boston, MA characterized Metastasis-Associated Protein 1 (MTA1) in CaP cell lines. MTA-1 is overexpressed in several tumor types and facilitates cancer through transcription repression. MTA-1 overexpression in LNCaP cells resulted in significantly increased ability for migration and invasion. MTA-1 overexpression resulted in upregulation of several genes associated with CaP progression.

Work from Vancouver, Canada presented by Dr. Hayashi discussed how the anti-apoptotic survival gene Clusterin upregulates the transcription factor NFk-B. Androgen-withdrawal is shown to up-regulate Clusterin expression. Using microarray techniques combined with small interfering RNA inhibition experiments NFk-B was identified to be under Clusterin regulation. This suggests that the NFk-B pathway may be a potential downstream effector of clusterin-mediated cytoprotective function.

By Christopher P. Evans, M.D.

UroToday - the only urology website with original content written by global urology key opinion leaders actively engaged in clinical practice.

To access the latest urology news releases from UroToday, go to:
http://www.urotoday.com

Copyright © 2006 - UroToday

Johns Hopkins Researchers Present Advances In Prostate Cancer Program At The Annual Meeting Of The American Urological Association

2007-04-16T02:43:00.001-07:00

Ciphergen Biosystems, Inc. (Nasdaq: CIPH) announced the discovery of two biomarkers that may aid in the management of prostate cancer, including for the detection, staging, and prediction of recurrence. These markers, a fragment of protein C inhibitor (PCI) and complement factor 4 (C4a), were identified in two separate studies, a multi-institutional study encompassing over 400 men and a five-year longitudinal study following 104 patients after radical prostatectomy. These studies demonstrated that PCI provides information useful for the detection and staging of prostate cancer, and the combined use of pre-surgery PCI, PSA, and C4a is predictive of prostate cancer recurrence. The work was performed by Dr. Daniel Chan and Dr. Zhen Zhang of the Johns Hopkins Medical Institutions as part of our research collaboration.

"We are pleased with the progress of our ongoing collaborative prostate cancer program with Johns Hopkins. These findings address a critical aspect of the management of prostate cancer, as the ability to predict recurrence can help physicians and patients understand better the aggressiveness of disease," said Gail S. Page, President and CEO of Ciphergen. "The discovery of PCI using Ciphergen's technology demonstrates its ability to identify markers directly related to the disease process, since PCI is present in seminal fluid and directly interacts with PSA. Further validation is underway."

About Ciphergen

Ciphergen is dedicated to translating protein biomarkers and panels of biomarkers into protein molecular diagnostic tests that improve patient care. We are also focused on providing collaborative R&D services through our Biomarker Discovery Center(R) laboratories for biomarker discovery for new diagnostic tests as well as pharmacoproteomic services for improved drug toxicology, efficacy and theranostic assays. Ciphergen develops, manufactures and markets a family of ProteinChip(R) Systems and services for clinical, research and process proteomics applications. ProteinChip Systems enable protein discovery, validation, identification and assay development to provide researchers with predictive, multi-marker assay capabilities and a better understanding of biological function at the protein level. Additional information about Ciphergen can be found at http://www.ciphergen.com.

Safe Harbor Statement

Note Regarding Forward-Looking Statements: This press release contains forward-looking statements. For purposes of the Private Securities Litigation Reform Act of 1995 (the "Act"), Ciphergen disclaims any intent or obligation to update these forward-looking statements, and claims the protection of the Safe Harbor for forward-looking statements contained in the Act. Examples of such forward-looking statements include statements regarding the usefulness of certain biomarkers to predict the recurrence of disease and the ability of Ciphergen to use such biomarkers in the creation of diagnostic tests. Actual results may differ materially from those projected in such forward-looking statements due to various factors, including the risk that Ciphergen may not be able to develop diagnostic tests based on the discoveries of certain biomarkers. Investors should consult Ciphergen's filings with the Securities and Exchange Commission, including its Form 10-K filed March 17, 2006, for further information regarding these and other risks related to the Company's business. Ciphergen, ProteinChip and Biomarker Discovery Center are registered trademarks of Ciphergen Biosystems, Inc.

Ciphergen Biosystems, Inc.
http://www.ciphergen.com/

Phase II Trial Of Trovax(R) In Prostate Cancer Commences - Oxford BioMedica

2007-04-16T01:52:00.001-07:00

Oxford BioMedica (LSE: OXB), a leading gene therapy company, announced today that a Phase II trial of TroVax in patients with prostate cancer that is unresponsive to hormone therapy is open for recruitment. This is the first clinical trial of TroVax in this cancer type.

The Phase II trial in prostate cancer is being conducted at the Methodist Hospital in Houston, Texas, USA. The Principal Investigator for the trial is Dr Robert Amato. The trial is designed to enrol 24 men with hormone-refractory prostate cancer who have previously received chemotherapy or have refused chemotherapy and have progressive disease. The trial is open label and will have two arms (12 patients each) to assess the activity of TroVax alone versus TroVax alongside an approved treatment for prostate cancer, granulocyte macrophage-colony stimulating factor (GM-CSF).

The primary objectives of the trial are to evaluate the safety and synergies of the combination treatment, and to assess whether GM-CSF, which is known to increase white blood cell count and hence boost the immune system, increases the anti-cancer immune response stimulated by TroVax. Efficacy endpoints include objective response rate, progression-free survival, overall survival and changes in prostate-specific antigen (PSA) level, which is a recognised marker of disease status.

Prostate cancer is the leading cause of cancer in men. Localised radiotherapy or surgery is potentially curative for early-stage disease although many patients relapse and require hormone therapy. However, therapeutic options are limited when the cancer has progressed and no longer responds to hormone therapy, which is the setting for the Phase II trial of TroVax. Initial data from this trial are expected in the first half of 2007. According to Datamonitor, treatments for prostate cancer generated worldwide sales of $2.7 billion in 2004.

Commenting on the start of the Phase II trial in prostate cancer, Oxford BioMedica's Chief Medical Officer, Dr Mike McDonald, said: "We are delighted that Dr Amato is supporting a Phase II trial of TroVax in prostate cancer. Given what we know of the product's safety profile and the anti-cancer immune response that it stimulates, we are hopeful that TroVax can provide a new therapeutic option for patients with prostate cancer who have progressed despite hormone therapy and for whom there are few available treatments."

Dr Robert Amato, Director of the Genitourinary Oncology Center at the Methodist Hospital said: "TroVax could provide a significant benefit to patients with hormone-refractory prostate cancer, particularly when administered with an effective immunostimulant such as GM-CSF. Our team at the Methodist Hospital has seen some intriguing clinical responses with TroVax from our trial in renal cell carcinoma and we are delighted to expand our collaboration with Oxford BioMedica into prostate cancer."

Oxford BioMedica's Chief Executive Officer, Professor Alan Kingsman added: "As we broaden and deepen the clinical development of TroVax, the value of our lead product candidate increases for potential partners."

Clinical evaluation of TroVax is ongoing in renal cell carcinoma, colorectal cancer and now prostate cancer. Oxford BioMedica plans to start a Phase III trial in renal cell carcinoma in the second half of 2006. The Company recently secured a Special Protocol Assessment agreement with the FDA for this Phase III trial. An update on the clinical trials and development plan for TroVax will be released to coincide with TroVax presentations at the American Society of Clinical Oncology (ASCO) Annual Meeting, to be held on 2-6 June in Atlanta, Georgia, USA.

Oxford BioMedica plc

Oxford BioMedica (LSE: OXB) is a biopharmaceutical company specialising in the development of novel gene-based therapeutics with a focus on the areas of oncology and neurotherapy. The Company was established in 1995 as a spin out from Oxford University, and is listed on the London Stock Exchange.

Oxford BioMedica has core expertise in gene delivery, as well as in-house clinical, regulatory and manufacturing know-how. In oncology, the pipeline includes an immunotherapy and a gene therapy in multiple Phase II trials, and a preclinical targeted antibody therapy in collaboration with Wyeth. In neurotherapy, the Company's lead product is a gene therapy for Parkinson's disease, which is expected to enter clinical trials in 2006, and four further preclinical candidates. The Company is underpinned by over 80 patent families, which represent one of the broadest patent estates in the field.

The Company has a staff of approximately 70 split between its main facilities in Oxford and its wholly owned subsidiary, BioMedica Inc, in San Diego, California. Oxford BioMedica has corporate collaborations with Wyeth, Intervet, Sigma-Aldrich, Viragen, MolMed, Virxsys and Kiadis; and has licensed technology to a number of companies including Merck & Co, Biogen Idec and Pfizer.

TroVax(R)

TroVax is Oxford BioMedica's leading cancer immunotherapy product. It is designed specifically to stimulate an anti-cancer immune response and has potential application in most solid tumour types. TroVax targets the tumour antigen 5T4, which is broadly distributed throughout a wide range of solid tumours. The presence of 5T4 is correlated with poor prognosis. The product consists of a poxvirus (MVA) gene transfer system, which delivers the gene for 5T4 and stimulates a patient's body to produce an anti-5T4 immune response. This immune response destroys tumour cells carrying the 5T4. TroVax has attracted external support from Cancer Research UK and the US National Cancer Institute. Over 100 patients have now been treated with TroVax in six clinical trials (collectively over 400 doses). The Company is targeting colorectal cancer and renal cell carcinoma (RCC) as lead indications for the development of TroVax. Renal cell carcinoma is an indication where TroVax might achieve a rapid route to product registration.

Prostate cancer

Prostate cancer is the leading cause of cancer in men. According to the American Cancer Society, an estimated 232,090 new cases of prostate cancer were diagnosed in the USA in 2005 and approximately 29,900 men die of this disease annually. The five-year survival rate of men with prostate cancer is 98%, although this falls to 34% for metastatic disease. Localised radiotherapy or surgery is potentially curative for early-stage disease although many patients relapse and require hormone therapy. According to Datamonitor, treatments for prostate cancer generated worldwide sales of $2.7 billion in 2004. However, therapeutic options are limited when the cancer has progressed and no longer responds to hormone therapy. Early detection is important, and it is recommended that men over the age of 50 have a prostate-specific antigen (PSA) blood test every year.

http://www.oxfordbiomedica.co.uk

Treatment Of First Patient With Picoplatin In Phase 1/2 Front-Line Prostate Cancer Trial

2007-04-16T01:42:00.001-07:00

NeoRx Corporation (Nasdaq: NERX), which is changing its name to Poniard Pharmaceuticals, Inc. effective June 16, 2006, today announced treatment of the first patient in a Phase 1/2 clinical trial evaluating picoplatin, the Company's lead product, for the potential front-line treatment of hormone-refractory metastatic prostate cancer.

"Picoplatin in combination with docetaxel [Taxotere(R)] may provide an effective treatment for patients with hormone-refractory metastatic prostate cancer, for whom docetaxel is the current standard of care," said Jerry McMahon, Ph.D., chairman and CEO of the Company. "Clinical trials have shown evidence of activity of picoplatin, including measurable responses, when administered as a single agent in the front-line treatment of hormone-refractory metastatic prostate cancer. Phase 1 study results have also indicated that picoplatin can be combined safely with docetaxel or paclitaxel. We believe the findings of the present Phase 1/2 study may support the broad use of picoplatin with taxanes, such as docetaxel and paclitaxel, and that the use of picoplatin as a front-line treatment will reduce the likelihood of chemoresistance associated with other marketed platinums."

Picoplatin is a new generation platinum therapy that provides a differentiated spectrum of activity and an improved safety profile. An intravenous chemotherapeutic agent, picoplatin is designed to overcome platinum resistance associated with the treatment of solid tumors. In addition to the trial in patients with hormone-refractory prostate cancer, picoplatin is being studied in an ongoing multi-center Phase 2 clinical trial in patients with small cell lung cancer and in a Phase 1/2 clinical trial as a potential front-line treatment for metastatic colorectal cancer.

Study Details

The Phase 1/2 study is evaluating picoplatin as front-line therapy in the treatment of patients with stage IV (metastatic) hormone-refractory prostate cancer who are newly diagnosed and have not received previous chemotherapy. The multi-center trial is designed to determine the safety and efficacy of picoplatin when administered every three weeks with docetaxel.

"Our past Phase 1 data support the use of picoplatin in combination with docetaxel or paclitaxel for the treatment of solid tumors. Picoplatin monotherapy has shown activity in a previous Phase 2 study in hormone-refractory prostate cancer. Because preclinical studies have demonstrated synergy for picoplatin plus taxane combinations, we believe that the combination of picoplatin plus docetaxel will be shown to be more effective in this Phase 2 clinical trial than either a taxane or picoplatin alone," said David A. Karlin, M.D., vice president of clinical development and regulatory affairs for the Company.

About Prostate Cancer

Prostate cancer is the most common type of cancer in men in the United States, apart from skin cancer, and the third leading cause of cancer death in men. An estimated 234,500 new cases will occur in the United States in 2006, and about 27,000 men will die of the disease, according to the American Cancer Society. In Europe, there are approximately 225,000 prostate cancer cases and 83,000 deaths annually, according to the International Agency for Research on Cancer's GLOBOCAN 2002 database.

Prostate tumors that have stopped responding to or are growing despite the use of active hormone treatment strategies are characterized as hormone-refractory. At that point, other options, such as chemotherapy, are often considered. Docetaxel, in combination with prednisone, was approved by the FDA in 2004 for the treatment of patients with hormone-refractory metastatic prostate cancer. The majority (more than 80 percent) of newly diagnosed stage IV patients who fail hormone therapy are currently treated with docetaxel either alone or in combination. Other options include mitoxantrone, estramustine or prednisone monotherapy as second-line treatment.

About NeoRx Corporation and Poniard Pharmaceuticals

On June 16, 2006, NeoRx Corporation will change its corporate name to Poniard Pharmaceuticals, Inc. A global specialty pharmaceutical company, Poniard Pharmaceuticals will focus on the discovery, development and commercialization of innovative oncology products to impact the lives of people with cancer. Picoplatin, the Company's lead product candidate, is a new generation platinum therapy that provides a differentiated spectrum of activity and an improved safety profile. An intravenous chemotherapeutic agent, picoplatin is designed to overcome platinum resistance associated with the treatment of solid tumors. Picoplatin currently is being studied in clinical trials for the treatment of small cell lung, colorectal and hormone-refractory prostate cancers. As part of its strategic goal of building a diverse oncology pipeline, the Company is collaborating with the Scripps Florida Research Institute on the discovery of novel, small-molecule, multi-targeted protein kinase inhibitors. For additional information please visit http://www.poniard.com or http://www.neorx.com.

This release contains forward-looking statements, including statements regarding the Company's business model, capital resources, discovery and development programs and clinical trial activities and results. The Company's actual results may differ materially from those indicated in these forward looking statements based on a number of factors, including anticipated operating losses, uncertainties associated with research, development, clinical trials and related regulatory approvals, future capital needs and uncertainty of additional financing, competition, uncertainties associated with intellectual property, dependence on third-party manufacturers, suppliers and collaborators, lack of sales and marketing experience, loss of key personnel, uncertainties associated with market acceptance, technology change and government regulation, and the other risks and uncertainties described in the Company's current and periodic reports filed with the Securities and Exchange Commission, including the Company's Annual Report on Form 10-K for the year ended December 31, 2005 and its Quarterly Report on Form 10-Q for the quarter ended March 31, 2006. Readers are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date of this release. The Company undertakes no obligation to update any forward-looking statement to reflect new information, events or circumstances after the date of this release or to reflect the occurrence of unanticipated events.

NeoRx Corporation; Poniard Pharmaceuticals
http://www.neorx.com/

New Combination Treatment Induces Regression Of Prostate Cancer

2007-04-16T00:45:00.001-07:00

A new treatment for prostate cancer may provide a distinct advantage over other conventional protocols and induce actual regression of the disease--not just relief from bone pain or a limited control of the disease, according to a study by Italian researchers released at SNM's 53rd Annual Meeting June 3-7 in San Diego.

"A new treatment protocol combining radionuclide therapy and chemotherapy may represent a distinct advantage over conventional protocols, especially when patients have metastatic (or spreading) prostate cancer that is not responding to hormonal therapy," said Giuliano Mariani, professor of nuclear medicine and director at the Regional Center of Nuclear Medicine at the University of Pisa Medical School in Italy. "Radionuclide therapy alleviated bone pain, but preliminary observations indicated that--if adequately combined with chemotherapy--it might produce clinical benefit in terms of regression and prolonged survival," added the co-author of "Early Response and Toxicity of 153Sm-EDTMP Combined With Docetaxel in Patients With Hormone-Refractory Metastatic Prostate Cancer."

All men are at risk of developing cancer in the prostate, a gland in the male reproductive system. Prostate cancer occurs when the cells of the prostate begin to grow uncontrollably, and these cells may spread--or metastasize--from the prostate to other parts of the body, especially the bones and lymph nodes, said Mariani. More than 234,000 men in the United States will be diagnosed with prostate cancer this year, and more than 27,000 will die of the disease, which is the second leading cause of cancer death in men.

"We explored combining radionuclide therapy based on the radioisotope Samarium-153 with carrier EDTMP and chemotherapy to achieve actual regression and prolonged survival," said Mariani. "Our research confirms the possibility of achieving tumor targeting of a radiopharmaceutical with such efficiency that it induces a definite therapeutic effect, and this shows the possibility of obtaining a synergistic therapeutic effect in combination with conventional chemotherapy," he explained.

"The blood toxic effects of our combination regimen were mild and comparable to those observed when the two therapies were used separately," said Mariani. In addition, researchers "observed significant reduction of PSA (prostate-specific antigen) levels in serum, a marker of the overall burden or severity of the disease," he added. "The majority of patients treated so far have either stable disease or regression of disease in a six-month follow-up," he noted.

"A major concern when attempting combination regimens of this type is to induce reciprocal augmentation of the possible toxic effects of the two therapies (radionuclide and chemotherapy), thus limiting applicability of the new protocol," said Mariani. "We are now evaluating our patients with an extended follow-up in order to assess the effect of the combined protocol on survival. Future investigations should explore the possibility of employing higher doses of the radiopharmaceutical in order to achieve the highest possible therapeutic effect--with the lowest possible toxic effect, he noted.

Maryann Verrillo
mverrillo@snm.org
Society of Nuclear Medicine
http://www.snm.org/

Data Presented At SNM Meeting Demonstrate New Potential For PROSTASCINT(R) Through Advances In Nuclear Medicine Imaging

2007-04-16T00:38:00.001-07:00

Cytogen Corporation (Nasdaq: CYTO) today announced the presentation of data from a series of studies with PROSTASCINT(R) (capromab pendetide), the first and only commercial monoclonal antibody-based agent that targets prostate-specific membrane antigen (PSMA) to image the extent and spread of prostate cancer. Results were presented at the 53rd Society of Nuclear Medicine (SNM) annual meeting taking place this week in San Diego, California.

"Advances in nuclear medicine imaging, such as the integration of anatomical and functional imaging, hastened the growth and widespread adoption of positron emission tomography (PET) imaging," said Michael D. Becker, president and chief executive officer of Cytogen. "Similar advances are now being utilized in SPECT imaging with novel molecular imaging agents such as PROSTASCINT as evidenced by the improved imaging quality reported by multiple centers at the SNM meeting. As with PET, these advances show the potential of fusion imaging with PROSTASCINT to improve outcomes for patients and demonstrated important technical and clinical advantages. We will continue to build on the role of PROSTASCINT as the backbone of our prostate-specific membrane antigen (PSMA) platform while driving our clinical development programs in therapeutic indications, such as CYT-500 for the treatment of hormone-refractory prostate cancer."

Fusion imaging with PROSTASCINT, or hybrid imaging, is an in vivo diagnostic technique that combines anatomic images with functional images. Anatomical information derived from either computed tomography (CT) or magnetic resonance (MR) imaging can be fused (or co-registered) with functional information obtained using single-photon emission computed tomography (SPECT) and novel molecular imaging agents, such as PROSTASCINT. SPECT imaging focuses on metabolic abnormalities that may be present earlier than the anatomical changes otherwise seen with CT or MR imaging alone. Co- registering anatomic and functional images provides an anatomic context for areas of enhanced or abnormal uptake, helping physicians identify areas of disease through enhanced image quality thereby enabling them to better plan an individualized treatment protocol for patients.

Highlights of the eight abstracts regarding fusion of PROSTASCINT scans with anatomical images provided by CT or MRI and new advanced image processing methods presented at the SNM meeting include:

"PROSTASCINT SPECT image quality is significantly improved by implementation of 3D OSEM with resolution recovery and attenuation and scatter correction (Abstract # 1436)"

The objective of this study was to determine if PROSTASCINT image quality can be significantly improved by applying resolution recovery techniques while simultaneously reducing image acquisition times.

PROSTASCINT studies were obtained on twelve consecutive patients and images were processed using filtered back projection (FBP), standard 3D-OSEM, and with software processing technology. The software implements a matched filtering technique to control noise, even when iterating enough to recover image features that are not obvious with standard processing. The full, three quarter and half count image sets reconstructed with the software were compared to the full count images processed with FBP and 3D-OSEM. In three patients who also had pelvic CT scans, the CT data sets were used to generate attenuation maps and attenuation correction (AC) and scatter correction (SC) were applied.

On subjective evaluation, software processing significantly improves the resolution and quality of PROSTASCINT images. CT attenuation and scatter correction provide further improvement. Software-processed images using half the total number of counts appeared superior to images processed with FBP and images using 75% of the counts were superior to images processed with 3D-OSEM. These findings suggest use of software processing would make it possible to significantly shorten acquisition times without compromising image quality.

"The advanced image resolution recovery techniques we evaluated using PROSTASCINT images allow physicians to visualize in greater detail the location and extent of disease, from both an anatomical and physiological perspective," said Michael Haseman, M.D., Nuclear Medicine physician with Radiological Associates of Sacramento in Sacramento, California one of the authors of the study. "These advances have the potential to simultaneously increase productivity for physicians and benefit patients by decreasing the amount of time for acquisition of a PROSTASCINT image."

"Improved disease detection with fusion of PROSTASCINT scans and multidetector CT (Abstract # 1040)"

Investigators from the Medical University of South Carolina reported results from one hundred and forty prostate cancer patients who underwent studies that combined the functional images from PROSTASCINT with the anatomic images provided by a multidetector CT. Their experience demonstrated that this combination provided increased specificity and sensitivity for delineation of residual prostate activity and blood vessels from lymphadenopathy and metastatic disease. Furthermore, the use of the multidetector CT decreased the number of required imaging sessions because it eliminated the need to use dual isotopes for determination of blood pool concentration.

"Retrospective diagnostic analysis of localized prostate cancer comparing needle core biopsy results to PROSTASCINT/SPECT fused with CT (Abstract # 1699)"

Investigators from the University Hospitals of Cleveland reported results from a retrospective analysis comparing fusion imaging with PROSTASCINT to needle core biopsy (NCB) results. Statistical analysis demonstrated agreement between NCB and PROSTASCINT. As expected, NCB identified a larger percentage of patients with disease than did PROSTASCINT, with PROSTASCINT sensitivity = 0.735. Since PSMA expression correlates with the aggressiveness of the tumor, the fact that 38% of patients in the study had Gleason scores below six may be causal in having inflated the PROSTASCINT rate of false negatives. These results indicate that localized prostate cancer diagnosis with PROSTASCINT may be utilized as an adjunct to NCB methods for identification of extracapsular extension, seminal vesicle with or without bladder involvement, and metastatic disease in other areas; and may prove particularly useful for the diagnosis of disease at sites where NCB cannot be safely performed.

"Unusual prostate metastasis to the brain: PROSTASCINT, CT, and MRI findings (Abstract # 1052)"

In a report from Yale New Haven Hospital, researchers presented a case of a solitary cerebral metastatic deposit detected by a PROSTASCINT scan in a patient with central nervous system symptoms whose only established malignancy was prostate carcinoma. CT and magnetic resonance imaging (MRI) demonstrated an abnormality corresponding to the same area of increased signal intensity with PROSTASCINT. The presence of cancer at the PROSTASCINT avid site was confirmed by biopsy.

"This is another instance corroborating the value of fusion imaging with PROSTASCINT," said Michael J. Manyak, MD, urologist and vice president of medical affairs for Cytogen. "Cerebral metastases from prostate cancer are unusual, but the strong correlation of fusion imaging with PROSTASCINT with clinical outcomes suggests that we now may be able to detect such unusual metastatic deposits."

"Hybrid imaging with single photon emission and x-ray computed tomography: Initial experience with 332 patients using an integrated 16-slice high-speed CT with a dual head SPECT device (Abstract # 1106)"

The integration of CT with positron emission tomography (PET) has already provided important technical and clinical advantages. New hybrid SPECT-CT devices (with high-speed CT) have been developed. The goal of this study by researchers at the Baptist Hospital of Miami is to relate the initial clinical applications and utilization patterns, and to describe the challenges and successes in implementing this new technology. Of one hundred and thirty general nuclear medicine procedures, nine were fusion imaging with PROSTASCINT performed using a 16-slice high-speed CT device coupled to a state-of-the-art dual-head nuclear imaging device. The study concluded that SPECT/CT fusion provides similar interpretive benefits as is afforded with hybrid PET/CT. In several clinical settings, the availability of CT can shorten image acquisition time and complexity.

"An eigenvalue based similarity measure and its application to tumor detection in nuclear medicine (Abstract # 1427)"

The objective of this study by researchers at King's College Hospital in London is to automatically detect significant differences between images acquired at either different times or with different radioisotopes for the purpose of automated tumor detection. In this approach, two co-registered sets of images are compared. One is assumed to be a tumor free reference data set, while the second image set may contain sites of abnormal PROSTASCINT uptake. Automated methods were used to assess degrees of change between the two sets of images. This approach to change detection is well suited to detecting small localized sites of uptake as demonstrated in detecting lymph node involvement in prostate cancer imaging using PROSTASCINT. The application of a locally adaptive eigenvalue based approach to change detection provides a sensitive and responsive approach to local image change detection and hence to tumor detection.

"Evaluation of quantitative image reconstruction methods for maximum lesion detectability in In-111 ProstaScint(R) prostate SPECT (Abstract # 347)"

The objective of this study by researchers at Johns Hopkins University and GE Healthcare with support from a DOD Idea Award and GE Research Grant, is to evaluate different quantitative image reconstruction methods for maximum lesion detectability with PROSTASCINT. Three distributions of uptake ratios in different organs in the abdomen and pelvical region, elliptically-shaped lesions of two different sizes (10x10x15 and 12x12x17 mm3) and lesion-to- background contrasts of 5:1 and 8:1 were used in a computer generated 3D NCAT phantom to simulate variations found in a patient population. Projections datasets were reconstructed using iterative OS-EM image reconstruction methods with four subsets and with different compensation methods: (1) no compensation, (2) with attenuation compensation (AC), (3) with AC and collimator-detector response (DC) compensation and (4) with AC, DC and scatter compensation (SC). Using optimum iteration numbers and cutoff frequencies statistically significant differences are found between all AUC curves except for those between the reconstruction methods (3) and (4). Results from the study indicate the clinical utility of quantitative image reconstruction methods for maximum lesion detectability with PROSTASCINT.

"Study of iterative SPECT corrective reconstruction methods for lesion detection and localization in In-111 PROSTASCINT imaging by means of combination of Monte-Carlo simulations and clinical evaluation techniques (Abstract # 540)"

Low contrast lesion detection is the main diagnostic task in prostate cancer imaging. The objective of this study by researchers at Johns Hopkins University with support GE Healthcare Research is to evaluate diagnostic properties of PROSTASCINT images obtained with corrective reconstruction techniques. Thirty clinical PROSTASCINT fusion imaging data sets acquired with routine protocol and found negative after clinical examination were used in this study. Patient specific attenuation maps acquired with low resolution CT (slice thickness of 1cm) were re-sliced to match the PROSTASCINT data. Three reconstruction strategies were compared: (1) OS-EM with attenuation compensation (AC) and post-filter parameters currently used at JHU for processing of PROSTASCINT studies, (2) OS-EM with AC and scatter compensation (SC), (3) OS-EM with AC, SC and geometric response (GRC) compensation and (4) RBI-MAP-EM with AC, SC and GRC. Three experienced clinicians participated in the study. One participant identified up to four possible lesion locations for each dataset using Xeleris(TM) (GE Healthcare, Waukesha, WI). The remaining observers reviewed combined images with lesions using Xeleris workstation. Reconstructed lesion contrast with options (2)-(4) was superior to the current clinically used OS-EM AC method. Inclusion of scatter and collimator-detector response modeling into iterative reconstruction were beneficial for lesion detection and localization in the context associated with PROSTASCINT.

About Prostate Cancer

Prostate cancer is the most common type of cancer found in American men, other than skin cancer. In 2006, the American Cancer Society estimates that there will be about 234,000 new cases of prostate cancer in the United States and that about 27,000 men will die from the disease. It is estimated that there are more than 2 million American men currently living with prostate cancer. Tests to determine the amount of prostate-specific antigen (PSA), a protein produced by the cells of the prostate gland, in the blood along with a digital rectal exam is used to help initially detect prostate cancer and is also used to monitor patients with a history of prostate cancer to see if the cancer has come back, or recurred. PSA levels cannot directly identify the extent or location of disease.

About PROSTASCINT

Cytogen's PROSTASCINT molecular imaging agent is the first and only commercial product targeting PSMA. PROSTASCINT consists of a monoclonal antibody (7E11.C5.3) directed against PSMA that is linked to the imaging radioisotope Indium-111. By targeting PSMA, the PROSTASCINT molecular imaging procedure can detect the extent and spread of prostate cancer using a standard gamma camera.

Cytogen is also developing CYT-500, a therapeutic product candidate using the same monoclonal antibody from PROSTASCINT combined with a higher affinity linker to attach a therapeutic as opposed to an imaging radionuclide. CYT-500 is designed to enable targeted delivery of a cytotoxic agent to PSMA- expressing cells. Cytogen expects to begin the first U.S. Phase I clinical trial of CYT-500 in patients with hormone-refractory prostate cancer during 2006.

PROSTASCINT is indicated as a diagnostic imaging agent in newly diagnosed patients with biopsy-proven prostate cancer, thought to be clinically localized after standard diagnostic evaluation and who are thought to be at high risk for pelvic lymph node metastases. PROSTASCINT is also indicated as a diagnostic imaging agent in post-prostatectomy patients with a rising PSA and a negative or equivocal standard metastatic evaluation in whom there is a high clinical suspicion of occult metastatic disease.

A copy of the full prescribing information for PROSTASCINT, including warnings, precautions, adverse events and other safety information, may be obtained in the U.S. from Cytogen Corporation by calling toll-free 800-833- 3533 or by visiting the Web site at http://www.cytogen.com, which is not part of this press release.

About PSMA

PSMA is a protein abundantly expressed on the surface of prostate cancer cells, with an increased expression in high-grade cancers, metastatic disease and hormone-refractory prostate cancer. PSMA is also present at high levels on the newly formed blood vessels, or neovasculature, needed for the growth and survival of many solid tumors. In contrast to other prostate-related antigens such as prostate-specific antigen (PSA), prostatic acid phosphatase (PAP) and prostate secretory protein, PSMA is a membrane glycoprotein that is not secreted. These unique attributes make PSMA an excellent target for monoclonal antibody diagnostic and therapeutic options in prostate and potentially other cancers. Clinical studies have also demonstrated that overexpression of PSMA determined by immunohistochemical staining using the 7E11.C5.3 antibody in primary prostate cancer not only correlates with other adverse traditional prognostic factors, but can independently predict disease recurrence.

ABOUT CYTOGEN CORPORATION

Founded in 1980, Cytogen Corporation of Princeton, NJ, is a biopharmaceutical company dedicated to improving the lives of patients with cancer by acquiring, developing and commercializing innovative molecules targeting the sites and stages of cancer progression. Cytogen's marketed products include QUADRAMET(R) (samarium Sm-153 lexidronam injection), PROSTASCINT(R) (capromab pendetide) kit for the preparation of Indium In-111 capromab pendetide, and SOLTAMOX(TM) (tamoxifen citrate, oral solution 10mg/5mL) in the United States. Cytogen's development pipeline consists of CYT-500, a therapeutic radiolabeled antibody targeting prostate-specific membrane antigen (PSMA), a protein highly expressed on the surface of prostate cancer cells and the neovasculature of solid tumors. Cytogen also has exclusive United States marketing rights to COMBIDEX(R) (ferumoxtran-10) for all applications, and the exclusive right to market and sell ferumoxytol (previously Code 7228) for oncology applications in the United States. Full prescribing information for the Company's products is available at http://www.cytogen.com or by calling 800-833-3533. For more information, please visit the Company's website at http://www.cytogen.com, which is not part of this press release.

ABOUT ROYAL PHILIPS ELECTRONICS

Royal Philips Electronics of the Netherlands is one of the world's biggest electronics companies and Europe's largest, with sales of $37.66 Billion (EUR 30.3 billion) in 2004. With activities in the three interlocking domains of healthcare, lifestyle and technology and 161,100 employees in more than 60 countries, it has market leadership positions in medical diagnostic imaging and patient monitoring, color television sets, electric shavers, lighting and silicon system solutions. News from Philips is located at http://www.philips.com/newscenter.

This press release contains certain "forward-looking" statements within the meaning of the Private Securities Litigation Reform Act of 1995 and Section 21E of the Securities Exchange Act of 1934, as amended. All statements, other than statements of historical facts, included in this press release regarding our strategy, future operations, financial position, future revenues, projected costs, prospects, plans and objectives of management are forward-looking statements. Such forward-looking statements involve a number of risks and uncertainties and investors are cautioned not to put any undue reliance on any forward-looking statement. There are a number of important factors that could cause Cytogen's results to differ materially from those indicated by such forward-looking statements. In particular, Cytogen's business is subject to a number of significant risks, which include, but are not limited to: the risk of obtaining additional capital; the risk of obtaining the necessary regulatory approvals; the risk of whether products result from development activities; the risk of shifts in the regulatory environment affecting sales of Cytogen's products such as third-party payor reimbursement issues; the risk associated with Cytogen's dependence on its partners for development of certain projects, as well as other factors expressed from time to time in Cytogen's periodic filings with the Securities and Exchange Commission (the "SEC"). As a result, this press release should be read in conjunction with Cytogen's periodic filings with the SEC. The forward-looking statements contained herein are made only as of the date of this press release, and Cytogen undertakes no obligation to publicly update such forward-looking statements to reflect subsequent events or circumstances.

Cytogen Corporation
http://www.cytogen.com/

Drug Attacks Prostate Cancer In Mouse Model By Destroying Its Blood Supply

2007-04-15T23:40:00.001-07:00

A medication used to treat other types of cancer strangles drug-resistant, metastatic prostate cancer by cutting off its blood supply, researchers from The University of Texas M. D. Anderson Cancer Center report in the June 7 issue of the Journal of the National Cancer Institute.

Imatinib, known commercially as Gleevec, worked best when combined with the chemotherapy paclitaxel to slash the incidence of bone metastases and the size of tumors in mice injected with a multiple-drug resistant form of prostate cancer. Tumors were found in only 4 of 18 mice treated with the combination, median tumor weight was one tenth of a gram, and the cancer spread to the lymph nodes in three cases. Tumors grew in all 19 control mice, their median tumor weight was 1.3 grams, and all metastasized to the lymph nodes.

This extremely drug-resistant form of the cancer, designed by the research team to emulate the grim clinical reality of prostate cancer that has spread into the bone, successfully warded off the combined medications in lab experiments, said Isaiah J. Fidler, D.V.M., Ph.D., chair of the Department of Cancer Biology and director of the Cancer Metastasis Research Center at M. D. Anderson.

"Why, then, did it work so well in the animal? Because we didn't attack the tumor, we attacked the blood vessels. We target and destroy the vasculature that provides oxygen and nutrients to tumor cells," said Fidler, the paper's senior author.

Fidler and colleagues show in the JNCI paper that imatinib killed tumor- related blood vessel (endothelial) cells by inactivating the platelet-derived growth factor receptors (PDGF-R) on the cell surface. This prevents the receptor's activation either by PDGF binding to it externally or by a signal generated internally by the cell.

Activation of PDGF-R stimulates the birth of new blood vessels, promotes cell division and migration, and inhibits a protective form of cell suicide known as apoptosis, all harmful effects in the service of a cancer cell.

With imatinib preventing activation of PDGF-R, Fidler said, the endothelial cells died by apoptosis first, with tumor cells following suit one to two weeks later.

Fidler said the findings are a vibrant example of the "seed and soil" hypothesis in metastasis -- the deadly spreading of a cancer from its organ of origin to other organs, a process that kills 90 percent of all patients who die from their disease.

In landmark findings, Fidler and colleagues demonstrated that the vast majority of cancer cells that depart a tumor die swiftly once in circulation and that metastases originate from less than 1 percent of a cancer's cells and even can arise from a single cell.

When these metastatic "seeds" enter circulation, they still need to find the exact microenvironment that permits them to grow. For prostate cancer, the second-leading cause of cancer death among men, that microenvironment is the bone.

Earlier research by Fidler and colleagues showed PDGF-R activation in metastatic prostate tumors adjacent to the bone but not in tumor cells next to muscle. PDGF-R also was activated in tumor-associated endothelial cells in the bone, but not in those blood vessel cells in neighboring muscle.

A JNCI paper by Fidler and colleagues in 2003 showed that blocking PDGF-R signaling in the mouse model of metastatic prostate cancer cut the incidence of cancer, reduced the size of tumors and incidence of metastasis.

The question was whether the combination of imatinib and paclitaxel achieved this by attacking the tumor itself or the tumor-related blood vessels. This week's JNCI paper answers that question: it kills the blood vessels first. "Here, we attack the soil. The seeds can be resistant. Kill the endothelial cell, you kill the soil," Fidler said.

Imatinib had an effect by itself, but the best result came from the pairing with paclitaxel, known commercially as Taxol, which induces apoptosis in non-resistant cancer cells. Taxol, developed by the Bristol-Myers Squibb Co., is frontline therapy for prostate cancer but eventually loses its effect as resistant tumor cells proliferate.

Gleevec, developed by Novartis Pharmaceuticals Corporation, is used to treat chronic myelogenous leukemia and gastrointestinal stromal tumors. Cancer cells are biologically diverse and genetically unstable, Fidler says, so it is highly unlikely that a single therapy will prevail, necessitating a multi-modal attack on the disease.

Paul Mathew, M.D., assistant professor, and Christopher Logothetis, M.D., professor and chair of the Department of Genitourinary Medical Oncology at M. D. Anderson, are leading a phase II clinical trial employing imatinib and docetaxel against androgen-independent prostate cancer. Docetaxel is in the same family of medication as paclitaxel.

This research project was funded by a Cancer Center Support Core grant and a Specialized Programs in Research Excellence (SPORE) grant, both from the National Cancer Institute of the National Institutes of Health. Fidler, Mathew and Logothetis have research projects that are sponsored by Novartis Pharmaceuticals.

Co-authors of the JNCI paper, all from M. D. Anderson, are: first author Sun-Jin Kim, M.D., Ph.D.; Hisanori Uehara, M.D., Ph.D.; Sertac Yazici, M.D.; Joseph Erik Busby, M.D.; Toru Nakamura, M.D., Ph.D.; Junqin He, M.D.; Marva Maya; Christopher Logothetis, M.D.; Paul Mathew, M.D.; Xuemei Wang; Kim-Anh Do, Ph.D.; and Dominic Fan, Ph.D.

University of Texas M. D. Anderson Cancer Center
http://www.mdanderson.org

Gene Discovery Opens Door To Tackling Disease

2007-04-15T23:36:00.001-07:00

Western Australian researchers have discovered a new gene that could lead to breakthroughs in breast and prostate cancer, as well as diabetes.

The gene, called SLIRP, was discovered by a team at the Western Australian Institute for Medical Research's (WAIMR) Laboratory for Cancer Medicine, led by Professor Peter Leedman, in collaboration with Professor Bert O'Malley's team at Baylor College of Medicine in Texas.

"When we baited our hook and went fishing in the breast cancer gene library we came up with SLIRP, much to our surprise, as this gene had not been characterised during the mapping of the human genome," said Professor Leedman.

"What's exciting is that SLIRP has the potential to shut down oestrogen in breast cancer cells and testosterone in prostate cancer cells.

"Most of those cancers depend on the hormones to stay alive, so if we can use SLIRP to block the hormones we may be able to help stop those diseases in their tracks."

Professor Leedman said the discovery could open the door to targeted new treatments for the cancers.

"If we can unravel the mystery of how SLIRP works to turn down the hormone action in cancer cells we could potentially develop so-called 'smart' drugs that zoom in on the gene," he said.

"The benefit is that 'smart' drugs can mean fewer nasty side effects for patients as they target specific genes, not entire areas of the body."

The find could also help researchers create blood tests to diagnose breast and prostate cancer.

"A breakthrough in the techniques available to diagnose breast and prostate cancer would hopefully allow for earlier detection and, importantly, lead to better survival rates," said Professor Leedman.

SLIRP has also been shown to turn down genes involved in energy metabolism.

"With its ability to turn off one of the key regulators of energy metabolism, SLIRP could well lead to progress in tackling diabetes and weight problems," Professor Leedman said.

The findings are to be published in the international journal, Molecular Cell, in June.

Professor Leedman and his team have now applied for a patent on the gene.

Professor Leedman, who is also deputy director of WAIMR, is recognized internationally for his work on hormones. Several funding bodies have contributed to this work, including the National Health and Medical Research Council, the National Breast Cancer Foundation, the Cancer Council of WA and the Royal Perth Hospital Medical Research Foundation.

Breast cancer is the most common cancer in Australian women, and about 2500 women and men die each year from breast and prostate cancer.

###

Contact: Natalie Papadopoulos
Research Australia

ASCO 2006 - GU Oral Presentation: Prostate Cancer

2007-04-15T22:42:00.001-07:00

UroToday.com - At the GU Oral Presentation, six prostate cancer abstracts were presented.

Stephenson, et al. presented a model for determining durable benefit of salvage external beam radiation therapy for post-prostatectomy patients with biochemical progression. The authors used multivariable Cox proportional hazard regression analysis in examining data on 1540 patients who underwent salvage external beam radiation therapy. The primary endpoint of the study was disease progression, either biochemical or clinical. The 5-year progression-free probability was 38% and the 10-year progression-free probability was 19%. The nomogram consisted of the following variables: pre-radiation therapy PSA, Gleason score at prostatectomy, neoadjuvant androgen deprivation, negative surgical margins, PSA at the time of biochemical progression, PSA doubling time, and regional nodal metastases. The concordance index for the nomogram was 0.68. The authors concluded that the nomogram reliably predicts outcome of salvage radiation therapy in patients with biochemical progression after prostatectomy.

Da Silva, et al. presented a randomized trial of continuous versus intermittent maximum androgen blockade (MAB) in patients with locally advanced or metastatic prostate cancer. A total of 766 patients were enrolled. After an initial induction of MAB, patients with significant reduction in PSA were randomized to continuous or intermittent MAB. Estimated 5 year survival was 51% for the continuous MAB group versus 53.8% for the intermittent MAB group (p=not significant). There was no statistically significant difference in objective or subjective progression between the 2 groups. Sexual activity and resultant quality of life were better in the intermittent MAB group. The authors concluded that intermittent androgen ablation should be an option for patients.

Patients with stage D2 prostate cancer are treated with androgen ablation therapy. SWOG 9346 (INT-0162) is an intergroup randomized trial of continuous versus intermittent androgen ablation therapy in patients with D2 prostate cancer. While the final results of this trial are forthcoming, Hussain et al. reported on the significance of the absolute PSA value after patients completed 7 months of induction androgen ablation. 1345 patients with D2 prostate cancer were included in this analysis. 1134 patients achieved a normalized PSA (<= 4.0 ng/mL) and 604 patients had an undetectable PSA at the end of induction. The median overall survival was 13 months for patients who did not normalize PSA, 44 months for patients with normalized but not undetectable PSA, and 75 months for patients with an undetectable PSA (these differences were statistically significant). The authors concluded that the absolute PSA value after 7 months of induction androgen ablation is a strong predictor of survival.

One of the drawbacks of androgen ablation therapy is loss of bone mineral density. Michaelson, et al. presented the results of a randomized trial in which 44 men with nonmetastatic prostate cancer undergoing androgen ablation therapy were randomized to receive an annual dose of zolendronic acid 4 mg by intravenous infusion or placebo. The primary endpoint was the effect on bone mineral density as measured by DEXA scan at one year. Patients who received the annual zolendronic acid had significantly increased bone mineral density of the total hip and spine at 1 year of follow-up. However, the study did not report on the impact of treatment on actual skeletal complications.

For patients who develop hormone refractory prostate cancer, systemic cytotoxic chemotherapy may play an important role. TAX 327 randomized patients with HRPC to docetaxel on an every 3 week schedule, docetaxel on a weekly schedule, or mitoxantrone (all arms included prednisone). TAX 327 demonstrated a survival advantage to docetaxel when administered on an every 3 week schedule. An ancillary analysis of TAX 327 was reported by Berthold et al. in which the authors determined the association between pain scores, quality of life scores, and PSA response in patients treated on this study. This study demonstrated that pain and quality of life were associated with PSA response, and pain response was an independent predictor of survival.

Beer et al. reported on the role of intermittent chemotherapy in the management of patients with HRPC. ASCENT was a multi-institutional randomized phase III trial comparing docetaxel plus DN-101 with docetaxel plus placebo. In this trial if patients had an excellent response to initial chemotherapy, they could elect to stop therapy with the option of further treatment in the future at the time of PSA progression. Eighteen percent of patients entered the intermittent phase of the treatment protocol. The median duration of the first chemotherapy holiday was 16 weeks. Upon resumption of docetaxel-based therapy on evidence of progression, 85% of patients demonstrated either a PSA response or stable disease. The promising results of this first prospective report of intermittent chemotherapy in HRPC should lead to further investigation of this approach.

Supported by an unrestrictional educational grant from Sanofi-Aventis.

By David Vaughn, MD

UroToday - the only urology website with original content written by global urology key opinion leaders actively engaged in clinical practice.

To access the latest urology news releases from UroToday, go to:
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Copyright © 2006 - UroToday

AUA 2006 - Prostate Cancer Staging II Podium Session

2007-04-15T22:37:00.001-07:00

UroToday.com - This session on staging addressed several areas of interest. With the growing stage shift in prostate tumors during the PSA era, concerns for overdetection of insignificant have grown. Several nomograms have been developed to contend with this issue and Currlin et al [ABST 1645] compared 10 available nomograms for there operational characteristics against a cohort of 646 patients with available clinical and histological data. The best fit to the clinical data was the Kattan (medium) nomogram with an area under the curve of 0.766. In general these tools were constrained by the limited specificity in the majority of cases.

The cancer of the prostate risk assessment (CAPRA) index from the University of California San Francisco underwent a multi-institutional validation Cooperberg et al [ABST 1648]. Compared to standard multivariable hazard models or nomograms, this index was developed from a community-based data base and follows a 0-10 scoring. Median follow up of the patients was 34 months and 26% of patients experienced a recurrence. The hazard ratio for each increase in point score1.39 95% [CI1.31-1.46]. 5 year actuarial recurrence free survival was 86% for scores of 0-1 and 21% for scores of 7-10. The validation of this model suggests that it may have significant application given its straight forward nature.

A reevaluation of clinical parameters and the potential for a positive bone scan was performed by Abbot et al [ABST 1652] in 467 prostate cancer patients diagnosed from 2000- 2004. Twenty three of 467 patients had a positive scan (4.9%). Only 2 patients with gleason score 7 or less disease were positive yet 16.7 percent of gleason 8-10 patients had positive scans. Further analysis suggested that the potential for a positive bone scan in gleason 7 or less patients was high only if the PSA value was greater than 30 ng/ml, while those patients with high gleason scores are at risk for a positive scan if the PSA exceeds 10ng/ml.

An effort at preoperative stratification for positive outcomes was demonstrated by Pierorazio et al [ABST 1653]. A subset of a university data based was analyzed for general PSA failure risk stratification as well as for urinary continence and erectile function. A linear analysis of all of these parameters was performed allowing an estimate of obtaining all or most of these positive outcomes. In the author's series, 71.2% of the low risk patients 52.3 % of the intermediate group patients and 47.5% of the high risk patients had the potential of obtaining excellent outcomes in all three categories (the "trifecta" per the authors). The analysis was based on a subset of patients and there was no validation or comparison with other series, yet such analysis do provide patients with a better understanding of appropriate expectations with surgery.

Fine and associates [ABST 1656] performed an analysis on the impact of minute gleason score 8-10 cancer on prostate needle biopsy. Consultant files revealed 108 patients with foci of high grade disease: 37 had Gleason 8, 41 Gleason 9 and 31 Gleason 10. Of the 42 patients who could be pathologically staged, 28/42 (66.7%) were organ confined, 7/42 had extracapsular extension with negative margins 5(11.9%) had ECE with positive margins and 2 had positive seminal vesicle or lymph node positivity. The progression free survival for these patients in different subgroups were excellent over 2-5 years (90.2% overall at 2years and 78% at five and 10 years) and 83.4 percent of patients demonstrated organ confined or ECE with negative margins. Surgery is clearly an option in a subset of these patients.

By S.Bruce Malkowicz, MD

WC 590

Supported by an unrestrictional educational grant from Sanofi-Aventis

UroToday - the only urology website with original content written by global urology key opinion leaders actively engaged in clinical practice.

To access the latest urology news releases from UroToday, go to:
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Copyright © 2006 - UroToday

AUA 2006 - Prostate Cancer Detection And Screening III

2007-04-15T21:39:00.001-07:00

UroToday.com - The role of PSA in the contemporary era and the impact of premalignant conditions on future diagnosis were some of the issues discussed in this section. Figler et al, [ABST 1473] investigated the value of PSA in detecting significant tumors. A cohort of 2067 patients spanning 1993 to 2004 were divided in two epochs [1993-98 and 1999-2004] and evaluated with respect to prostate volume, percent Gleason grade 4/5, overall estimated tumor volume. The preoperative PSA value was positively correlated to tumor volume, volume of high grade disease and tumor gleason grade in both epochs suggesting that there is still contemporary predictive power in a PSA value. A family history of prostate cancer has classically been demonstrated in 15% of younger patients. Hood and associates, [ABST 1483] reviewed a cohort of 724 patients and identified 66 patients under the age of 50. Overall the entire cohort had a family history of prostate cancer in 33.8% of patients. In the younger cohort 28/66 [42.2%] patients had a family history defined as a first or second degree relative. 88% of patients had pathologic stage T2 disease and the majority of patients 44/66 [67%] had Gleason score 6 disease. These data suggest that the early evaluation of younger patients with a family history is clearly warranted.

Patel and colleagues [ABST 1487] reported on a longitudinal follow up of patients with high grade prostatic intraepithelial neoplasia (HGPIN). The method of follow up was empiric and consisted of an interval prostate needle biopsy every 2-3 year even in the absence of PSA of DRE changes. The records of 100 such patients were reviewed and demonstrated a cancer diagnosis rate of 30%. These patients were diagnosed at a median follow up of 32 months. 22/30 were diagnosed after the first biopsy and the remainder on the second biopsy. 29 or 30 men had T1c disease and 12/30 had gleason 7 or greater grade tumors. There was a strong concordance between the site of the original HGPIN diagnosis and the site of cancer diagnosis 21/30 cases. The majority of cases were detected in the peripheral zone (27 of 30. This association with location supports the proposition that HGPIN is a premalignant lesion and underscores the value of routine follow-up biopsies.

Atypical small acinar proliferation or ASAP is an entity regularly noted on prostate needle biopsies and associated with the detection of cancer at a later date. Flury et al [ABST 1492] evaluated prostates from cystoprostatectomy specimens and in a review of evaluable cases 24/65 demonstrated prostate cancer. Nine cases demonstrated high grade PIN and ASAP or ASAP alone. The use of serial sectioning and special stains demonstrated that the majority of these ASAP cases (8/9) could indeed be diagnosed as cancer. These findings suggest that an aggressive clinical evaluation of these lesions is warranted. In an evaluation of evolving technology a report on 117 patients undergoing 11C-PET was described by Seitz et al. [ABST 1498]. In the detection of a primary malignancy a sensitivity of 86.8% and sensitivity of 59.1% was recorded. In the case of metastatic spread a sensitivity of 80% and specificity of 95.1% was noted. It was suggested that the combined use of CT/PET may be of value in the detection of metastatic spread of prostate cancer but this will require further study.

In a further evaluation of the role of body mass index (BMI) an evaluation of the CaPSURE data set identified 6692 men with appropriate data Meng, et all [ABST 1507]. A higher BMI was associated with a lower serum PSA and a larger measured prostate volume. This was independent of age and year of diagnosis. This paradoxical association may have some impact regarding the detection of disease and disparities in treatment outcomes noted so far when trying to evaluate this parameter.

WC 648

Supported by an unrestrictional educational grant from Sanofi-Aventis

By S.Bruce Malkowicz, MD

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Copyright © 2006 - UroToday

AUA 2006 - Prostate Cancer Localized III Discussed Poster Session

2007-04-15T21:35:00.001-07:00

UroToday.com - Interesting topics in this section included investigations to evaluate the appropriateness of focal therapy, the natural history of treated disease and the outcomes of some significant clinical trials. Barber et al [ABST 1573] evaluated the characteristics of patients with a single positive core with regard to contralateral disease. The single core was defined as 40 percent or less, or 5mm or less, of one core among 6-12 cores of tissue. These were collected from 1999 to 2004. 129 cases were identified and 46 (35.6%) underwent a radical prostatectomy. The average tumor volume was 1.15 cc's and the largest tumor focus was on the ipsilateral side of biopsy. However 89% of cases demonstrated tumor on the contralateral side and one forth of these had high grade disease. These data suggested that a 6-12 core biopsy may be insufficient to rule out contralateral disease. Another perspective is that greater stringency in defining a single core (smaller percentage of core positive or absence of high grade tumor) as informative for ipsilateral disease is needed.

In an evaluation of 961 radical prostatectomy specimens, tumor foci were ranked according to size Ohori, et al [ABST 1574] Mean tumor volume for the largest site was 2.13 cc with significantly reduced volumes for the next several lesions(0.39,0.17,0.09, 0.04 cc's) in succession. 16% of cases demonstrated extracapsular disease and over 85% of these where associated with the largest lesion. Only 18% of lesions in patients with a PSA under 10 were unifocal, yet in the majority of such patients, treatment of this lesion would eradicate 80-90% of the significant tumor. The authors suggest that there may be some role for unifocal therapy for disease control in specific situations.

Longitudinal recurrence of PSA after radical prostatectomy was described by Allaf et al [ABST 1582] who analyzed the biochemical progression of 3521 radical prostatectomy patients treated from 1986 to 2005. With a mean follow up of 7 years the biochemical failure rate was 13%. 60.9% of failures occurred within 5 years and 91% and 97% occurred within 10 and 15 years. Patients with favorable pathological features failed later and only 23.8% of biochemical recurrences had occurred by 5 years. These data suggest that the vast number of biochemical failure will manifest themselves over the first 10 years of follow-up.

Docetaxel is now the standard for the therapy of hormone refractory, metastatic prostate cancer. Major areas of research are now aimed at improving outcomes in these patients by augmenting this platform with other agents or investigating whether this platform can be shifted to earlier stage disease. Kibel et al, [ABST 1587] described a multi-institutional trial of weekly docetaxel for high risk patients after radical prostatectomy. Risk was assessed by a multivariate hazards model and those patients with a greater than 50% risk of biochemical or clinical recurrence. 77 patients were enrolled and at a median follow up of 28 moths 63% of the patients' demonstrated progression. Median progression free survival was 16 months compared to a predicted 10 months. Four of seven deaths were attributable to prostate cancer. Grade I-II toxicity in the absence of greater toxicity was noted in 70% of patients yet 26% had grade III toxicity and one GI bleed and a case of pulmonary fibrosis and death from pneumonia may have been treatment related. These data suggest that adjuvant docetaxel in prostate cancer is feasible. The toxicity can be significant yet is generally tolerable. Progression free survival appears longer than predicted by nomogram. Based on these data an adjuvant phase III trial has been initiated.

The potential side effects of androgen deprivation therapy have become increasingly of concern as a larger proportion of men without bone metastatic disease remain on therapy. Changes of bone mineral density and increased fracture risk are of significant concern. Casey et al [ABST 1590] reported on a trial of 200 men with bone metastasis negative disease who received either goserelin acetate every three months for one year or goserelin acetate and 4mg of zoledronic acid on the same schedule. The primary end point was the BMD change in the lumbar spine from baseline over this period and other bone sites were also measured. An interim analysis of 80 patients demonstrated a 2% decrease in BMD in those patients receiving goserelin alone and an average 4% increase in patients receiving zoledronic acid and goserelin. These data suggest that this combination can prevent bone loss in those patients receiving hormonal therapy.

Supported by an unrestrictional educational grant from Sanofi-Aventis

By S.Bruce Malkowicz, MD

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Copyright © 2006 - UroToday

Repeat Corticosteroids For Pregnant Women At Risk Of Preterm Delivery Could Be Beneficial

2007-04-15T20:39:00.001-07:00

Giving pregnant women at risk of preterm delivery repeat doses of corticosteroids* can reduce illness in their newborn babies, suggest the results of an early trial in this week's issue of The Lancet.

Premature babies have a high risk of lung disease and breathing difficulties (respiratory distress syndrome). A single course of corticosteroids before premature delivery is the most effective known strategy of reducing respiratory illness in these babies. Some previous studies suggest that repeating the dose of prenatal corticosteroids may be beneficial for babies but others have reported adverse side effects, including growth problems, infection after birth, and abnormal development in childhood.

To investigate the effectiveness and safety of repeat corticosteroids, Caroline Crowther (Women's and Children's Hospital, North Adelaide, SA, Australia) and colleagues recruited 982 pregnant women at risk of preterm birth into their trial. The women were less than 32 weeks pregnant and had received a single dose of corticosteroids 7 or more days before. The team randomly assigned participants to receive a repeat injection of corticosteroids or a placebo every week until 32 weeks of pregnancy, if they remained at risk of a preterm birth. The researchers followed-up the babies until discharge from hospital and found that fewer babies had respiratory distress syndrome (186 vs 239 / 33% vs 41%) or severe lung disease (65 vs 114 / 12% vs 20%) in the repeat corticosteroids group than in the placebo group. Babies exposed to repeat corticosteroids also needed less oxygen therapy and help breathing. The investigators did not find any difference in the weight, length, and head circumference of the babies in the two treatment groups.

Professor Crowther states: "These short-term benefits for the babies in our study support the use of repeat doses of corticosteroids in women who remain at risk of very preterm birth 7 or more days after an initial course." The authors say longer-follow up is needed to see if repeat prenatal corticosteriods have any long-term effects.

###

Contact: Professor Caroline A Crowther, Department of Obstetrics & Gynaecology, University of Adelaide, Women's and Children's Hospital, 72 King William Road, North Adelaide, SA 5006, Australia. caroline.crowther@adelaide.edu.au

Contact: Joe Santangelo
Lancet

Race Affects Prostate Cancer Survival Rates

2007-04-15T20:36:00.001-07:00

Japanese American men respond better to hormonal treatment for prostate cancer and have a much higher survival rate than white American men, according to research published in the latest issue of the UK-based urology journal BJU International.

A team of researchers from the US and Japan compared 59 white males and 105 Japanese American males who had receive hormone treatment for prostate cancer at The Queen's Medical Centre in Honolulu, Hawaii.

They discovered that, although there was little difference between the patients' backgrounds and ages, five years after the treatment started the overall survival rate for the Japanese American patients was 66 per cent, compared with 42 per cent for the white men in the sample.

The result between the two ethnic groups did not appear to be affected by whether the men's cancer was confined to the prostate or had spread to other parts of the body.

However the survival rates tended to even out in the most advanced cancers, when the levels of the Prostate-Specific Antigen (PSA) protein produced by the prostate exceeded 100. About a quarter of the study sample had PSA readings in this range.

"Japanese men have one of the lowest rates of prostate cancer worldwide, but levels tend to be higher among Japanese American men, compared with those who actually live in Japan" says lead author Dr Takashi Fukagai, a urologist at the Showa University School of Medicine in Tokyo.

"One theory is that Japanese Americans retain some native Japanese genetic and,or,lifestyle characteristics that lead to them developing prostate cancer less frequently than white American men.

"We also have a ongoing study of other ethnic groups, which has shown that Chinese men living in Hawaii have a similar prognosis to Japanese American men. We have also discovered that Filipino men have a worse prognosis than those two ethnic groups, but still enjoy a higher survival rate than white men.

The men who took part in the study had an average age of 76 and had all received hormonal treatment from the same team or urologists. Hormone therapy blocks the action of the male sex hormones that help the cancer cells grow, either through administering testosterone lowering drugs or by removing the testosterone-producing testicles.

None of the study subjects had received definitive surgical or radiation therapy.

Five factors were examined in detail - age, race, pre-treatment PSA score, the clinical stage that the cancer had reached and the Gleason score, which defines the severity of the cancer based on microscopic analysis.

Only two factors - race and the pre-treatment PSA score - were shown to have a significant effect on whether the patient survived and for how long.

"One of the reasons why the survival rate may be better among Japanese American men with a PSA of less than 100 is that they are less likely to suffer from the side-effects of the hormone treatment, such as heart problems, compared with white American males" adds Dr Fukagai.

ґ "There is also evidence that different races have different genetic profiles. As prostate cancer is a disease that is affected by hormones, it may be that the nature of the actual disease, and how it progresses, varies between different races.

"However prostate cancer undergoes various changes as it develops and we suspect that the changes that take place in the advanced stages of the disease reduce the effect of those ethnic differences.

"This would account for the fact that there was a difference in survival rates between Japanese American and white men with a PSA of less than 100, but those ethnic differences disappeared in more severe cases with a PSA of more than 100."

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Phase I Sudy Combining Gefitinib With Docetaxel And Estramustine Reported

2007-04-15T19:38:00.001-07:00

UroToday.com - Combination docetaxel regimens have been shown to improve overall survival in randomized clinical trial in patients with hormone-refractory prostate cancer (CaP). Gefitinib is an oral epidermal growth factor receptor inhibitor (EGFR). It is active against CaP cell lines and xenografts. Given alone, gefitinib was not highly active in hormone-refractory CaP patients. Dr. Wilding and associates from 5 institutions report a Phase I trial of gefitinib combined with docetaxel and estramustine in patients with hormone refractory CaP. The results appear in epub format of the journal Cancer.

Two doses of gefitinib (250mg/day and 500mg/day) in combination with docetaxel and estramustine were evaluated in escalating groups of 15 patients each. Tolerability and toxicity are the primary endpoints of a Phase I trial.

No dose limiting toxicities were observed. Gefitinib related adverse events included diarrhea (23 patients), rash (8 patients), nausea (7 patients), dry skin (6 patients) and emesis (6 patients). Pharmacokinetic analysis suggested that docetaxel and estramustine had no effect on gefitinib levels. Gefitinib had no effect on docetaxel at the 250mg/day dose, but decreased exposure at the 500mg/day dose. At the 500mg dose, it appeared that gefitinib increased exposure to estramustine.

Of the 22 evaluable patients, 9 experienced a pain response. A PSA response was found in 9 of 30 patients evaluable for this endpoint. A partial objective tumor response was identified in 1 of 13 evaluable patients in each dose group. The median time to progression for both doses combined was 185 days.

While toxicity and tolerability was reasonable with the combined regimen, the additional clinical benefit of gefitinib to the other agents was not convincing.

By Christopher P. Evans, MD

Reference:
Cancer. 2006 May 1;106(9):1917-24.
Link Here.
Wilding G, Soulie P, Trump D, Das-Gupta A, Small E

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Prostate Adjustable Continence Therapy (ProAct) Is A Safe And Effective Treatment For Post Radical Prostatectomy Incontinence

2007-04-15T19:36:00.001-07:00

UroToday.com - Urinary incontinence after radical prostatectomy may affect 3-8% of patients and can have a significant negative impact on a patient's quality of life. Although the artificial urinary sphincter is considered the "gold standard" treatment for post prostatectomy incontinence, not all patients are candidates or wish to undergo this procedure. Some will opt for an alternative such as the male sling or periurethral bulking agent. Trigo-Roch and colleagues from Sao Paulo, Brazil examined the safety and efficacy of a new prosthesis the Prostate Adjustable Continence Therapy (ProAct; Uromedica, Plymouth, Minn) for the treatment of post prostatectomy incontinence.

This system consists of two balloons placed para-urethrally just beneath the bladder neck. There is a titanium port, which is placed in the scrotum, connected to each of the balloons that allow postoperative adjustment of the balloon volumes. They studied 25 patients with post radical prostatectomy incontinence. The device was placed under anesthesia through a perineal incision. With the help of fluoroscopy the pelvic floor is perforated and the region lateral to the urethra in the area of the bladder neck is dilated to create room for the balloon. A radio-opaque marker on the balloon tip allows identification of the exact position of the balloon. Once in the proper place, 1.5-2.0 ml of x-ray contrast and sterile water is injected into the balloon. Operative time was 22-58 minutes. 2 bladder perforations occurred at the time of placement, and these were treated with catheter drainage for 3 days. There were no other significant complications.

Of the 25 patients undergoing the procedure, 23 were evaluated (1 was lost to follow-up and 1 died). Pad count decreased from 4.76 ± 1.71 to 1.83 ± 1.58. Mean quality of life questionnaire (IQOL) scores improved from 63.04 ± 20.42 to 82.59 ± 15.24. There was also an increase in Valsalva leak point pressure after ProAct treatment from 48.7±25.37 cm H2O to 84.1 ± 33.5 cm H2O. Overall 8/23 (35%) were not satisfied with their treatment or had no significant change. The average number of postoperative adjustments performed in the outpatient setting was 4.6. 17.3% of the patients required revision (2 were for reimplantation of a single balloon after unintended bladder perforation, 1 was for a leaking balloon, 1 was for removal for erosion of injection port through the scrotal skin). Mean follow up was 22. 4 months (range 6-48 months).

The authors conclude that ProAct periurethral implant is a safe and effective alternative for the treatment of post radical prostatectomy incontinence. In those who failed or were not satisfied after ProAct treatment and went on the artificial urinary sphincter placement, the removal of the balloons were performed at the same setting and did not increase the difficulty of the procedure. This may add another treatment option for this difficult situation, however as the authors point out, larger series with longer follow up will be needed to determine its viability.

By M. Louis Moy, MD

Reference:
Urology 2006; 67: 965-969
Link Here.
Trigo-Rocha F, Gomes CM, Pompeo AC, Lucon AM, Arap S

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Duloxetine Proven Effective For Use In Men With Stress Urinary Incontinence After Radical Prostatectomy

2007-04-15T18:39:00.001-07:00

UroToday.com - Up to 33% of patients undergoing radical prostatectomy suffer from varying degrees of incontinence. The rate of incontinence after cystectomy and neobladder creation may be higher. The therapy for this incontinence includes pelvic floor exercises, the use of incontinence devices such as pads or condom catheters, the endourethral injection of bulking agents, or finally the placement of a male sling or an artificial urinary sphincter.

Duloxetine is a combined serotonin and norepinephrine reuptake inhibitor. As a consequence, the activity of the striated sphincter muscle increases. Duloxetine has been shown to effectively treat women with stress and mixed type incontinence. Recently, a study by B. Schlenker, C. G. Stief and colleagues from Munich Germany examined the role of duloxetine in the treatment of male patients suffering from stress urinary incontinence (SUI) after radical prostatectomy or radical cystectomy. The study is published in the June 2006 issue of European Urology.

Over a two-year period, 18 patients with SUI post radical prostatectomy or radical cystectomy with orthotopic neobladder were treated with 40 mg of duloxetine twice daily. The average number of pads pre-treatment was 8 a day. After an average of 9.4 weeks of pharmacotherapy with duloxetine, the average number of pads fell from 8.0/day to 4.2 pads/day (p < 0.0001). Fifteen of the 18 patients (83.33%) reported improvement of SUI after the use of duloxetine and 7 of 18 patients (39%) were completely dry or used one pad per day at the most for safety reasons. The mean pad use in these patients before duloxetine was 3.9 pads/day.

Six patients reported no side effects at all; the majority reported mild side effects such as fatigue (4), dry mouth (3), nausea (1), or insomnia (1). Most of the side effects vanished within 4 weeks but 6 patients (33.3%) discontinued the medication due to adverse events.

The preliminary results from this pilot study suggest good efficacy of duloxetine for the treatment of SUI in men post pelvic surgery. The side effect profile of the drug did lead to the drop out of 1/3 rd of patients however. The patients must be educated on the high incidence of the main side effect of massive fatigue or insomnia.

By Michael J. Metro, MD

Reference:
Eur Urol. 2006 June; 49 (6):1075-78
Link Here.
Schlenker B, Gratzke C, Reich O, Schorsch I, Seitz M, Stief CG

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Predictive Model Of Prostate Cancer Risk From The PCPT

2007-04-15T18:36:00.001-07:00

UroToday.com - Combining PSA with other risk factors for prostate cancer (CaP) may result in individualized risk prediction. In the April 19, 2006 issue of the Journal of the National Cancer Institute, Dr. Ian Thompson and colleagues report a predictive model for CaP based upon the Prostate Cancer Prevention Trial (PCPT) database.

PCPT included 18,882 men with a normal rectal exam and PSA level in a study of chemoprevention using finasteride or placebo over a 7-year period. At the end of the 7-year study period, participants in the placebo group who underwent prostate biopsy were included in this report. CaP risk modeling was performed using risk variables such as family history of CaP, race, PSA, DRE, previous biopsy history, age, and PSA velocity. Multivariable logistic regression model analyzed the data.

The study cohort consisted of 5,519 men. Most were Caucasian, and did not have a previous biopsy. Variables statistically associated with an increased risk of CaP included increasing PSA, positive family history, and abnormal DRE. Having a previously negative prostate biopsy was linked to a statistically decreased risk of CaP.

Interestingly, PSA velocity was associated with a 6-fold increase in CaP risk by itself, but in combination with the above significant variables neither PSA velocity nor patient age added independent prognostic information. African Americans had a 40% increased risk of CaP, which was just statistically significant.

The authors point out that the report is limited by patient characteristics not reflecting those of the general population.

By Christopher P. Evans, MD

Reference:
J Natl Cancer Inst 2006; 98:529-34.
Link Here.
Thompson IM, Ankerst DP, Chi C, Goodman PJ, Tangen CM, Lucia MS, Feng Z, Parnes HL, Coltman CA Jr

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Review Identifies Factors That Influence Patient Treatment Choice For Localized Prostate Cancer

2007-04-15T17:39:00.001-07:00

Common Genetic Prostate Cancer Variant Is Identified

2007-04-15T17:36:00.001-07:00

Establishing An Integrated Molecular Signature Model For Metastatic Prostate Cancer

2007-04-15T16:39:00.001-07:00

Symptom Severity Of PBS/IC Difficult To Predict Based On Medical History And Demographics

2007-04-15T16:35:00.001-07:00

In A Phase III Lipid Interim Analysis, ACAPODENE Treatment Lowered Cholesterol And Raised HDL In Prostate Cancer Patients On Androgen Deprivation

2007-04-15T15:39:00.001-07:00

GTx, Inc. (Nasdaq: GTXI), the Men's Health Biotech Company, announced today the results of a lipid interim analysis of the pivotal Phase III ADT clinical trial evaluating oral, once daily ACAPODENE(R) (toremifene citrate) 80mg for the treatment of the multiple serious side effects of androgen deprivation therapy (ADT) in men with advanced prostate cancer.

The lipid interim analysis was performed in the first 197 subjects who completed one year of the trial. Prostate cancer patients on ADT who received ACAPODENE compared to placebo had lower total cholesterol (-7.1%; p=0.001), LDL (-9.0%; p=0.003), and triglyceride (-20.1%; p=0.009) levels, a reduction in the total cholesterol/HDL ratio (-11.7%; p<0.001), and higher HDL levels (+5.4%; p=0.018). Although patients who were also taking statins had further reduction of total cholesterol, the magnitude of these lipid changes was greater in patients who were not concomitantly taking statins. The final lipid data set will be evaluated before any conclusions may be made on the clinical significance of these findings.

"Androgen deprivation therapy is quite effective in turning prostate cancer into a chronic disease in many patients," said Matthew R. Smith, M.D., Ph.D., Associate Professor of Medicine, Harvard Medical School. Dr. Smith is the lead Principal Investigator of the Phase III ADT clinical trial. "As patients are living longer with prostate cancer because of ADT, serious side effects have become major causes of morbidity and even death. These serious ADT side effects include osteoporosis and fractures as well as adverse lipid changes and cardiovascular disease. A medicine that is able to address multiple side effects of ADT would mark important progress in the care of prostate cancer patients."

GTx is conducting a pivotal Phase III clinical trial of ACAPODENE for the treatment of multiple serious side effects of ADT in approximately 1,400 men at over 150 sites in the United States and Mexico. The primary endpoint of the trial is a reduction in vertebral fractures. Secondary endpoints include improvements in bone mineral density (BMD), hot flashes, gynecomastia, and lipid profiles. Final data from the trial, which is being conducted under a Special Protocol Assessment with the United States Food & Drug Administration, is expected in the second half of 2007.

In December 2005, GTx conducted an interim analysis of the bone loss that leads to fractures which is another serious side effect of ADT. BMD was measured in the first 197 patients to complete one year of treatment. The per protocol analysis revealed highly statistically significant increases in BMD in all three skeletal sites assessed in patients receiving ACAPODENE compared to placebo: lumbar spine (+2.3%; p<0.001); hip (+2.0%; p=0.001); and femoral neck (+1.5%; p=0.009). The magnitude of these positive changes in BMD provides increased confidence that ACAPODENE should show efficacy in the trial's primary endpoint, a 40% reduction in vertebral fractures at two years.

"ACAPODENE has demonstrated the potential to increase bone mineral density, and the lipid interim analysis suggests that ACAPODENE may lower cholesterol," said Mitchell S. Steiner, M.D., CEO of GTx. "We continue to be confident in the Phase III ADT clinical trial. If ACAPODENE can treat multiple serious side effects of ADT, it has the potential to become the mainstay of prostate cancer supportive care for patients on ADT."

About GTx

GTx, headquartered in Memphis, Tenn., is a biopharmaceutical company dedicated to the discovery, development and commercialization of therapeutics for cancer and serious conditions related to men's health. GTx's lead drug discovery and development programs are focused on small molecules that selectively modulate the effects of estrogens and androgens, two essential classes of hormones. GTx is developing ACAPODENE(R) (toremifene citrate), a selective estrogen receptor modulator, or SERM, in two separate clinical programs in men: first, a pivotal Phase III clinical trial for the treatment of serious side effects of ADT for advanced prostate cancer, and second, a pivotal Phase III clinical trial for the prevention of prostate cancer in high risk men with high grade prostatic intraepithelial neoplasia, or PIN. GTx also is developing ostarine, a selective androgen receptor modulator, or SARM, for a variety of indications including muscle wasting and bone loss in frail elderly patients, osteoporosis, muscle wasting in end stage renal disease patients, and severe burn wounds and associated muscle wasting. GTx has licensed to Ortho Biotech Products, L.P., a subsidiary of Johnson & Johnson, another of its SARMs, andarine, under a joint collaboration and license agreement.

Forward-Looking Information is Subject to Risk and Uncertainty This press release contains forward-looking statements based upon GTx's current expectations. Forward-looking statements involve risks and uncertainties. GTx's actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of these risks and uncertainties, which include, without limitation, the risks that (i) GTx will not be able to commercialize its product candidates if clinical trials do not demonstrate safety and efficacy in humans; (ii) GTx may not be able to obtain required regulatory approvals to commercialize its product candidates; (iii) GTx's clinical trials may not be completed on schedule, or at all, or may otherwise be suspended or terminated; and (iv) GTx could utilize its available cash resources sooner than it currently expects and may be unable to raise capital when needed, which would force GTx to delay, reduce or eliminate its product development programs or commercialization efforts. You should not place undue reliance on these forward-looking statements, which apply only as of the date of this press release. GTx's Quarterly Report on Form 10-Q filed on May 5, 2006 contains a more comprehensive description of these and other risks to which GTx is subject. GTx expressly disclaims any obligation or undertaking to release publicly any updates or revisions to any forward-looking statements contained herein to reflect any change in its expectations with regard thereto or any change in events, conditions or circumstances on which any such statements are based.

GTx, Inc.
http://www.gtxinc.com

New Test Detects Prostate Cancer Spread At The Earliest Time

2007-04-15T15:35:00.001-07:00

A new prognostic test can help determine whether a prostate cancer patient will go on to have a recurrence of the disease, even if surrounding lymph nodes initially appear negative for cancer, according to a study by University of Southern California researchers.

The test, developed at USC, "appears to be a very powerful test and better than anything else we know of for predicting recurrence," says Richard Cote, professor of pathology and urology at the Keck School of Medicine of USC. Current trials are also using the test to find hidden metastases in lymph nodes and bone marrow for breast and lung cancers.

The study, "Detection of Occult Lymph Node Metastases in Patients with Local Advanced (pT3) Node-Negative Prostate Cancer" appears this week in the Journal of Clinical Oncology.

Prostate cancer is the most common non-skin cancer in America, according to the Prostate Cancer Foundation. One in six American men will be diagnosed with prostate cancer, making men 35 percent more likely to be diagnosed with prostate cancer than women are to be diagnosed with breast cancer.

"Thanks to greater awareness, as well as increased and improved screening, we see men increasingly diagnosed with prostate cancer in its early stages," Cote says. "Most of these patients will do very well and will not require treatment beyond surgery or radiation therapy to cure their disease."

But a proportion of these patients have metastases of the prostate cancer appear later, even when the lymph nodes removed at the time of the cancer surgery appeared negative for cancer, he says.

Cote and his colleagues looked at 3,914 lymph nodes from 180 patients who were staged as having lymph nodes negative for cancer based on standardized histologic evaluation (visual scan under a microscope). The lymph nodes were then evaluated for occult (hidden) metastases using new specific immunohistochemistry tests that can detect cancer on a cell-by-cell level.

Their new analysis checks for cells that react with antibodies to cytokeratins and PSA. The team's testing found occult tumor cells in the lymph nodes of 24 of the patients whose lymph nodes had been previously been diagnosed as cancer-free.

The test used to detect the occult tumor cells is more sensitive than any clinical, pathologic or radiographic techniques, Cote says.

The group then compared cancer recurrence and survival in those patients with the hidden tumor cells versus those without the cells. The presence of occult tumor cells was associated with increased prostate cancer recurrence and decreased survival. In fact, "the outcome for patients with occult tumor cells was similar to those who were identified as having positive lymph nodes at the time of the surgery," Cote says.

"We have shown that occult tumor spread in lymph nodes is a significant predictor of disease recurrence," he says. "Once surgery is performed, the primary form of treatment is adjuvant systemic therapy. In patients with no evidence of metastasis, success of such therapy is assumed to be due to killing of occult tumor before it becomes clinically evident. Therefore, the ability to detect occult metastasis is pivotal to identification of patients who would most benefit from systemic therapy and also identify patients who may be spared from unnecessary therapy."

###

Vincenzo Pagliarulo, Debra Hawkes, Frank Brands, Susan Groshen, Jie Cai, John P. Stein, Gary Lieskovsky, Donald G. Skinner, Richard J. Cote, "Detection of Occult Lymph Node Metastases in Patients with Locally Advanced (pT3) Node Negative Prostate Cancer," Journal of Clinical Oncology, 24: 2735-2741, 2006.

Contact: Jon Weiner

University of Southern California

Urologist Plays Key Role In Determining Use Of Hormone Therapy In Prostate Cancer

2007-04-15T14:39:00.001-07:00

The urologist a patient sees may be a more important factor than the tumor characteristics or the patient's other characteristics in determining the use of hormonal therapy for prostate cancer, a new study reports in the June 21 issue of the Journal of the National Cancer Institute.

Androgen deprivation therapy, which blocks steroid hormones called androgens, is used in around 50% of prostate cancer patients. It is recommended for locally advanced and metastatic prostate cancer. Because the therapy is expensive and potentially toxic, it is important to understand the factors responsible for its use.

Vahakn B. Shahinian, M.D., from the University of Texas Medical Branch in Galveston, and colleagues analyzed data from 61,717 men in the Surveillance, Epidemiology, and End Results (SEER) -- Medicare database who were diagnosed with prostate cancer at age 65 years or older and from their 1,802 urologists. The scientists assessed the pattern of androgen therapy use within 6 months of diagnosis to determine the part attributable to the urologist versus patient and tumor characteristics.

The authors found that the use of androgen deprivation therapy for prostate cancer was more dependent on the urologist who treated the patient than characteristics of the tumor or patient. They report that 21% of variance in the use of androgen deprivation therapy could be attributed to the urologist, versus 9.7% to tumor characteristics (stage or grade), and 4.3% to patient characteristics.

The authors write, "The substantial variance in use of androgen deprivation therapy attributable to the urologist, independent of patient factors, suggest that interventions at the level of the urologist may be an effective way to modify the use of this therapy for prostate cancer."

In an accompanying editorial, Paul F. Schellhammer, M.D., of Eastern Virginia Medical School in Norfolk, Va., discusses the challenges of using androgen deprivation for prostate cancer therapy. He writes, "The challenge for urologists is to offer men with high-risk, potentially lethal prostate cancer androgen deprivation therapy early in their course of treatment and to avoid the unnecessary risks of androgen deprivation therapy among men with low-risk indolent disease."

###

Contacts:

* Article: Vahakn B. Shahinian, vbshahin@utmb.edu
* Editorial: Paul F. Schellhammer, schellpf@evms.edu

Citations:

* Article: Shahinian VB, Kuo Y-F, Freeman JL, Goodwin JS. Determinants of Androgen Deprivation Therapy Use for Prostate Cancer: Role of the Urologist. J Natl Cancer Inst 2006; 98: 839-845.
* Editorial: Schellhammer PF. Timing of Androgen Deprivation Therapy: Some Questions Answered, Others Not. J Natl Cancer Inst 2006; 98:802-803.

Note: The Journal of the National Cancer Institute is published by Oxford University Press and is not affiliated with the National Cancer Institute. Attribution to the Journal of the National Cancer Institute is requested in all news coverage. Visit the Journal online at http://jncicancerspectrum.oxfordjournals.org/

Contact: Ariel Whitworth

Journal of the National Cancer Institute

Dutasteride Induces Apoptosis In Androgen Sensitive Prostate Cancer Cell Lines

2007-04-15T14:36:00.001-07:00

UroToday.com - Dr. McCrohan as research colleagues from University College Dublin report that the dual 5 a-reductase inhibitor dutasteride induces apoptosis in androgen sensitive, but not androgen insensitive prostate cancer (CaP) cell lines and primary cultures. Their work appears in the epub version of Cancer.

The administration of dutasteride (0.1-10mM) resulted in apoptosis in androgen sensitive LNCaP, pwR-1E, PNT-2 and PC3 (AR) cells. Apoptosis was assessed by quantification of cells with hypodiploid DNA by propidium iodide incorporation. LNCaP and PC3 (AR) cells remained responsive to treatment to 4 and 5 days, respectively. Androgen insensitive PC3 cells did not respond to dutasteride.

In first passage CaP primary cultures, dutasteride induced apoptosis in 7 samples, but not in 9 samples. The difference could not be explained by differences in dutasteride on cell cycle progression or expression of 5 a-reductase isoforms.

The Reduction by Dutasteride of Prostate Cancer Events study is testing dutasteride as chemoprevention and this basic science work adds to the understanding of dutasteride mechanism. It also provides rationale for use of dutasteride in combination with intermittent androgen deprivation therapy, now being tested in clinical trials.

By Christopher P. Evans, MD
Reference:
Cancer. 2006 Jun 15;106(12):2743-52
Link Here.
Maria McCrohan A, Morrissey C, O'keane C, Mulligan N, Watson C, Smith J, Fitzpatrick JM, Watson RW

UroToday - the only urology website with original content written by global urology key opinion leaders actively engaged in clinical practice.

To access the latest urology news releases from UroToday, go to:
http://www.urotoday.com

Copyright © 2006 - UroToday

High Surgeon Radical Prostatectomy Volume Is Linked To Lower Hospital Charges

2007-04-15T13:39:00.001-07:00

UroToday.com - Increased procedure volume by both surgeon and hospital are associated with decreased mortality. In the on-line version of European Urology, 2006 Dr. Ramirez and colleagues report that increased surgeon radical prostatectomy (RP) volume is associated with decreased hospital charges.

Using the State of Florida Inpatient Discharge Information Data File, 3,167 RPs were identified between January and December 1998. The average patient age was 63.5 years and 77% of patients were Caucasian. Of note, in 1997 the average surgical volume for RPs was 18.

Hospital charges ranged from $4,755 to $140,201 with a mean of $18,200. SV ranged from 2 to 162 with a mean of 68 RPs. The multivariate regression indicated that a SV increase corresponding to one RP is linked with a $25 decrease in hospital charges.

Application of this observation to a theoretical cohort of 1,000 patients suggests that one surgeon performing 50 RPs annually versus one performing 10 RPs results in $1,000 of increased hospital charges. This would correspond to a savings of $1,000,000 if applied to 1,000 patients.

Using the 1997 SV average of 18, 1,000 RPs performed by 10 surgeons with an annual volume of 200 instead of 18 would result in decreased charges of $4,550,000.

This study is limited by selection bias in the patient sample and does not include the variable of hospital volume. In addition, charges do not necessarily reflect true savings.

By Christopher P. Evans, MD

Reference:
Eur Urol. 2006 Jul;50(1):58-63. Epub 2006 Mar 27.
Link Here.
Ramirez A, Benayoun S, Briganti A, Chun J, Perrotte P, Kattan MW, Graefen M, McCormack M, Neugut AI, Saad F, Karakiewicz PI

UroToday - the only urology website with original content written by global urology key opinion leaders actively engaged in clinical practice.

To access the latest urology news releases from UroToday, go to:
http://www.urotoday.com

Copyright © 2006 - UroToday

Shift In Prostate Cancer Gleason Grades From 1989 To 2001

2007-04-15T13:36:00.001-07:00

UroToday.com - Since the clinical introduction of PSA testing, there is reason to hypothesize that prostate cancer (CaP) Gleason grades may have shifted due to a variety of factors. Dr. Sengupta and associates at the Mayo Clinic report this to be the case in the epub version of Cancer.

Between 1989 and 2001, 8750 patients who underwent radical prostatectomy at the Mayo clinic met the study criteria. Gleason grades over the 13 year period were reviewed and biochemical recurrence (defined as a PSA >0.4ng/ml) was recorded. Biochemical recurrence-free survival (BRFS) was estimated using Kaplan Meier methodology.

The percentage of RP specimens assigned a Gleason grade of 3 as either the primary or secondary grade increased from 86% vs. 49% for primary and 71% vs. 47% for secondary pattern for 1999-2001 vs. 1989-1999, respectively. During the same time periods, the prevalence of Gleason grade 2 tumors decreased from 0.4% vs. 38% for primary and 1.3% vs. 28% for secondary Gleason grade patterns. As a result, less Gleason score 4-5 tumors and more Gleason score 6-7 tumors were identified.

The BRFS for patients with Gleason score 6 and 7 tumors improved over the time periods. For Gleason score 6 the 5-year BRFS improved form 47% to 87% over the two time periods. For Gleason score 7 the 5-year BRFS improved form 51% to 66% over the two time periods. There were no significant changes noted over the same time periods for Gleason scores 2-4 or 8-10. In multivariate analysis, improved BRFS remained for Gleason score 6, but not for patients with Gleason score 7 tumors.

The noted Gleason grade shifts may be a result of true stage migration secondary to PSA screening or changes in pathologic interpretation over the time period studied.

By Christopher P. Evans, MD

Reference: Cancer. 2006 Jun 15;106(12):2630-5.

Link Here.

Sengupta S, Slezak JM, Blute ML, Leibovich BC, Sebo TJ, Myers RP, Cheville JC, Bergstralh EJ, Zincke H. UroToday - the only urology website with original content written by global urology key opinion leaders actively engaged in clinical practice.

To access the latest urology news releases from UroToday, go to:
http://www.urotoday.com

Copyright © 2006 - UroToday

Obesity Undermines Radiation Treatment For Prostate Cancer

2007-04-15T12:39:00.001-07:00

Obese men do not benefit from radiation treatment for prostate cancer as much as men who are not obese, say researchers from the University of Texas M.D. Anderson Cancer Center, Houston. This could help doctors decide how aggressive certain people's treatment should be.

Prof. Sara Strom, lead author, said "Prostate cancer for most men is quiet. It's a cancer with a good outcome. Basically, what you would like in prostate cancer is to identify men who have more chances of having a bad outcome, so you can do something different with them. Obesity is something to take into consideration."

You can read about this report in the journal Cancer, August 1.

However, some experts have questioned the validity of the report for two reasons:

1. The study refers to treatment carried out between 1998-2001. New radiation technologies have changed since then.
2. The number of obese men is the study was small.

Several studies have indicated that obesity is a complicating factor in many different cancers and their treatment outcomes. Men who are obese and get prostate cancer are more likely to suffer from the more aggressive forms. Prostate cancer patients who are obese have a much higher probability of having to have either the whole prostate or parts of it surgically removed (prostatectomy).

This is the first study to specifically look at how obesity may affect prostate cancer progression after radiation treatment. Prof. Storm and team looked at the medical records of 873 men who had prostate cancer - they had only received external beam radiotherapy for their disease. 5% of the men were either moderately or severely obese while 18% were mildly obese.

The researchers found a clear correlation between prostate cancer progression and the patients' body mass index (BMI). The higher a patient's BMI, the higher the likelihood of metastasis or tumor recurrence. They also found that the 5% who were moderately to severely obese were 99% more likely to have high levels of prostate-specific antigen.

Storm said that they found that after taking all other important risk factor for a bad outcome into consideration, obesity remained a significant risk factor, not only of rising PSA levels, but also with cancer recurrence and metastasis. The researchers are not sure why this may be the case.

Abstract
Influence of obesity on biochemical and clinical failure after external-beam radiotherapy for localized prostate cancer

The research was funded by the National Cancer Institute (NCI); Grant Number: CA84964, CA90270, NIEHS ES07784

The research team:

Sara S. Strom, PhD
Department of Epidemiology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas
Ashish M. Kamat, MD
Department of Urology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas
Stephen K. Gruschkus, MPH
Department of Epidemiology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas
Yun Gu, PhD
Department of Epidemiology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas
Sijin Wen, MS
Department of Biomathematics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas
Min Rex Cheung, MD, PhD
Department of Radiation Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas
Louis L. Pisters, MD
Department of Urology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas
Andrew K. Lee, MD
Department of Radiation Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas
Charles J. Rosser, MD
Department of Urology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas
Deborah A. Kuban, MD
Department of Radiation Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas

Written by: Christian Nordqvist
Editor: Medical News Today

Obesity In Prostate Cancer Patients Predicts Cancer Recurrence And Progression

2007-04-15T12:36:00.001-07:00

Obesity in a patient is an independent predictor of whether localized prostate cancer will progress following radiotherapy treatment, say researchers at M. D. Anderson Cancer Center.

In a study reported in the Aug. 1 issue of the journal Cancer, researchers found that moderately and severely obese patients had a 99 percent greater risk of developing biochemical failure (an early marker of cancer progression) than other patients. The study also reports that obese patients had a 66 percent increased risk of having a tumor that recurs or becomes metastatic than did non-obese patients.

This finding mirrors results from a parallel study by M. D. Anderson researchers, reported last year in Clinical Cancer Research, that found that a history of weight gain or obesity at the time of diagnosis also played a role in how aggressive prostate cancer may become after surgery.

"Together, these studies confirm that a man's body mass index (BMI = weight/height2) can be a significant factor in how well he fares after standard treatments for prostate cancer," says the lead researcher of both studies, Sara Strom, Ph.D., an associate professor in the Department of Epidemiology.

"The fact that the same association was found among patients with different risk profiles, and who were treated with different therapies, would suggest that poorer outcomes in obese men are not related to differences in treatment as much as to differences in tumor behavior between obese and non-obese men," she says.

Strom adds that these findings suggest that obese prostate cancer patients should be followed more closely after treatment. "When patients and their physicians are uncertain about the need for further therapy, our research indicates that a man's weight should be factored into that decision," she says.

According to Strom, the study is the first to examine the relationship between obesity and prostate cancer progression after primary therapy with external beam radiotherapy, a common treatment option. The researchers sought to determine whether obesity is an independent predictor of biochemical failure - a rising prostate specific antigen (PSA) level that can indicate advancing cancer - and they also wanted to know if the cancer actually progressed among those patients.

To conduct the study, the scientists examined the records of 873 patients whose prostate cancer was locally confined, and who were treated with radiotherapy at M. D. Anderson between 1988 and 2001. Of these patients, 18 percent were mildly obese and 5 percent were moderately to severely obese.

They found that patients who were obese tended to be diagnosed with prostate cancer at an earlier age than patients who were not obese, and also that African-American men had the highest obesity rates.

After an average follow-up period of 96 months, 295 patients experienced biochemical failure, and cancer recurred in 127 of these patients.

After adjusting for clinical and treatment variables among patients, the researchers found that BMI significantly predicted whether a patient would experience both rising PSA and a return of prostate cancer. For example, biochemical failure occured more quickly with increased BMI: an average of 30 months for patients with normal weight, and 26 months for patients deemed moderately to severely obese. Researchers also found that when comparing obese patients with non-obese patients, obese men had a significantly higher rate of cancer recurrence.

Strom and her colleagues cannot yet say why excess BMI contributed to cancer progression, or whether losing weight after a prostate cancer diagnosis will make any difference in outcome. "But by knowing this association, we may be able to design rational preventive strategies," she says.

###

Co-authors of the study, which was funded by the National Cancer Institute, are all from M. D. Anderson. They are Ashish Kamat, M.D.; Stephen Gruschkus; Yun Gu, Ph.D.; Sijin Wen; Rex Min Cheung, M.D., Ph.D.; Louis Pisters, M.D.; Andrew Lee, M.D.; Charles Rosser, M.D.; and Deborah Kuban, M.D.

Contact: Stephanie Dedeaux
University of Texas M. D. Anderson Cancer Center

For Men With Prostate Cancer, Treatment Information Fails To Address Fears

2007-04-15T11:39:00.001-07:00

Men with prostate cancer make emotionally driven treatment decisions influenced by anecdote and misconception rather than consideration of clinical trial evidence, according to a new study. Published in the August 1, 2006 issue of CANCER (http://www.interscience.wiley.com/cancer-newsroom), a peer-reviewed journal of the American Cancer Society, the study reveals that fear and uncertainty drove initial treatment decisions seeking rapid results, and that there was little interest in seeking second opinions. Furthermore, patient decisions were influenced by misconceptions about disease management options, and men often erroneously applied the anecdotal experiences of others with prostate cancer to their own circumstances, even when the severity of their own disease and available treatment options were significantly different.

While there are several treatment options for men with localized prostate cancer, clinical trials have failed to demonstrate one optimal therapy. Each treatment option has benefits and its own unique and significant adverse side effects. Radical prostatectomy, for example, has only minimal survival benefits compared to even observation, but is associated with complications, such as impotence and urinary incontinence. With no clear-cut medical guidance, patients must assume a greater role in deciding on treatment in the face of disquieting statistics and risk-benefit information.

To characterize the factors that influence men's treatment decisions, Thomas Denberg, M.D., Ph.D. of the University of Colorado at Denver and Health Sciences Center and colleagues interviewed 20 men newly diagnosed with localized prostate cancer before and after treatment.

Three factors characterized the patients' decisions: fear and uncertainty; misconceptions about treatment efficacy and risks; and anecdotal information about other's experiences with prostate cancer. Even though most patients knew prostate cancer grows slowly, such "abstract knowledge did little to dispel the vividly frightening, yet unlikely prospect of prostate cancer suddenly 'blossoming,'" the researchers write.

After urologists reviewed the risks and benefits of the treatment options, patients had poor recall of the information they were provided, often confused side effects and treatments, and often said that the side effects had no impact on their treatment decision. Sixteen of 20 men did not intend to seek a second opinion, generally because of misconceptions about its purpose.

Dr. Denberg and his colleagues report that "this study illustrates that while attention to health information, outcome preferences, and the framing of numerical risk is necessary, it is hardly sufficient for achieving quality in patient-centered decision-making." It is important to give greater attention to patients' fears, misconceptions, and anecdotal influences.

###

Article: "Patient Treatment Preferences in Localized Prostate Carcinoma: The Influence of Emotion, Misconception, and Anecdote," Thomas D. Denberg, Trisha V. Melhado, John F. Steiner, CANCER; Published Online: June 26, 2006 (DOI: 10.1002/cncr.22033); Print Issue Date: August 1, 2006.

Contact: David Greenberg
John Wiley & Sons, Inc.

Breast Cancer Drug To Extend Lives Of Men With Late Stage Prostate Cancer

2007-04-15T11:36:00.001-07:00

Today, the National Institute of Health and Clinical Excellence (NICE), UK, releases guidance that recommends that all eligible patients have access to a prostate cancer drug[1] - a move that will affect the lives of thousands of men across the UK[2].

Taxotere® (docetaxel) - which has been routinely given to female patients with late stage breast cancer since 2001[3] - extends the lives of men with late stage prostate cancer (metastatic hormone refractory prostate cancer - mHRPC) and improves their quality of life[4].

Prostate cancer is the most common cancer of men in the UK; over 30,000 men are diagnosed with the condition each year[5]. In addition, it is the second most common form of cancer death, annually killing over 10,000 men - that's approximately one death every hour[2]. Although data is limited, it is believed that the majority of these deaths are due to late stage prostate cancer[6]. Late stage prostate cancer is a form of prostate cancer in which patients have become resistant to conventional treatments (hormone therapy).

Patients and patient groups welcome today's guidance and are calling for all men who could benefit to be given immediate access to the treatment, which could extend their lives and improve their quality of life for their remaining months. "NICE guidance supporting the use of Taxotere (docetaxel) based regimens for women with late stage breast cancer has been available since 2001," says John Anderson, CEO, Prostate Research Campaign UK. "It's about time that men are also able to get to the front of the queue to gain equal access to a treatment that could benefit them. Now that the guidance has arrived there is no excuse for men who could benefit not to get access as quickly as possible. "

"Taxotere (docetaxel) is the first treatment to improve survival, improve quality of life and reverse progress of metastatic hormone refractory prostate cancer," Professor Nick James, Consultant Clinical Oncologist, University Hospital Birmingham NHS Trust (Queen Elizabeth Cancer Centre), Birmingham and UK principal investigator on TAX 327. "Now that NICE have supported the use of this treatment, we urge all PCTs to ensure that funding is available for all patients whom could benefit. It is now up to patients to make sure that they are asking for this treatment, clinicians to offer it and PCTs to fund it."

"The provision of Taxotere (docetaxel) is one of the most important advances in treating late stage prostate cancer that has occurred in recent years," says John Anderson, Consultant Urological Surgeon, Sheffield. "Now that we have been able to demonstrate that Taxotere is able to extend survival and manage quality of life in late stage prostate cancer, exciting trials have been initiated which will examine the benefits of Taxotere in early stage prostate cancer."

NICE's guidance was based on the highly influential TAX 327 trial, published in a well-respected journal, the New England Journal of Medicine, in October 2004. The trial found that Taxotere® (docetaxel), plus prednisolone (prednisone), improved overall patient survival by 24%. Median patient survival with the Taxotere based regimen was 18.9 months compared to 16.5 months for the standard treatment (mitoxantrone).

Taxotere® (docetaxel) is recommended, within its licensed indications, as a treatment option for men with hormone-refractory metastatic prostate cancer only if their Karnofsky performance-status score is 60% or more. The Karnofsky score is a measure of quality of life factors.

Taxotere® (docetaxel) has an acceptable increase of side effects. The most commonly reported adverse reaction associated with Taxotere® (docetaxel) is neutropaenia (low white cell count, which may lead to infection), which is reversible and not cumulative[7].

Other common side effects include flushing, skin rash, chest tightness, back pain, anaemia, nausea, sore mouth and taste change, diarrhoea, hair loss, hypersensitivity and tiredness.

http://www.sanofi-aventis.com

-------------------------------------------------------------

[1] National Institute for Health and Clinical Excellence (NICE). Guidance: Docetaxel for treatment of hormone-refractory metastatic prostate cancer. June 2006. Available from: http://www.nice.org.uk

[2] Cancer Research UK. Prostate Cancer Mortality Statistics.
Accessed: June 2006.

[3] National Institute for Health and Clinical Excellence (NICE). Guidance: Taxanes for the treatment of breast cancer. Review 30. Available from: http://www.nice.org.uk

[4] Tannock IF et al. Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med. 2004, 351:1502

[5] Cancer Research UK. Prostate Cancer Incidence Statistics.
Accessed: June 2006.

[6] National Institute of Health and Clinical Excellence (NICE). Docetaxel for the treatment of hormone-refractory metastatic prostate cancer (overview). 2005. Available from: http://www.nice.org.uk

[7] Taxotere Summary of Product Characteristics (May 2006)

Obesity Is Associated With Less Favorable Outcome After Radiation Therapy For Prostate Cancer

2007-04-15T10:39:00.001-07:00

Obese men with prostate cancer are at higher risk for treatment failure after primary radiation therapy, according to a new study. Published in the August 1, 2006 issue of CANCER (http://www.interscience.wiley.com/cancer-newsroom), a peer-reviewed journal of the American Cancer Society, the study reveals that each incremental increase in body mass index (BMI) increased the risk for clinical or biochemical failure. The study is the first to investigate the association between obesity and post-radiotherapy outcome.

Evidence has increasingly shown that obesity has a deleterious effect on the human body, from the risk of diabetes to joint disease. Obesity has more recently been shown to play a significant role in the development of some cancers, including cancers of the breast, prostate, colon, and many others. Obesity has also been associated with the progression of disease. Obese men with prostate cancer often have more aggressive disease and higher mortality rates. Researchers postulate that fat tissue influences concentrations of various significant signaling molecules, such as testosterone, estrogen, insulin and insulin-like growth factor, which play a role in prostate cancer development and progression.

There is already a body of scientific evidence demonstrating that obesity is linked to treatment failure after prostatectomy. However, there are no data on the effects of obesity on the effectiveness of radiation treatment for prostate cancer. Sara Strom, Ph.D. of the University of Texas M. D. Anderson Cancer Center in Houston and colleagues reviewed the medical records of 873 patients who received radiotherapy alone for prostate cancer. Among the group, 18 percent were mildly obese and 5 percent were moderately to severely obese.

After an average 96 months of follow-up, 295 of the men had three consecutive increases in blood PSA, indicating biochemical failure. Meanwhile, 127 of the men had clinical failure (local recurrence and/or distant metastasis) determined by radiologic studies, biopsy, or physical examination. On analysis, risk of biochemical and clinical failure were influenced by BMI. As BMI increased, the risk of disease progression following therapy also increased. For example, men who were moderately or severely obese were at double the risk for biochemical failure than other men who were not.

The authors conclude, "our findings validate the importance of obesity in prostate cancer progression and suggest a link to the biology of this tumor."

To understand the influence of obesity on treatment and possibly exploit that understanding to improve treatment outcome, "future studies should evaluate the relationship of obesity with dietary factors, genetic modifiers of steroid androgen metabolism, insulin, and a detailed investigation of the insulin growth factor pathway to explore the underlying mechanisms of action in prostate carcinogenesis," suggest the authors.

###

Article: "Influence of Obesity on Biochemical and Clinical Failure After External-Beam Radiotherapy for Localized Prostate Cancer," Sara S. Strom, Ashish M. Kamat, Stephen K. Gruschkus, Yun Gu, Sijin Wen, Min Rex Cheung, Louis L. Pisters, Andrew K Lee, Charles J Rosser, Deborah A. Kuban, CANCER; Published Online: June 26, 2006 (DOI: 10.1002/cncr.22025); Print Issue Date: August 1, 2006.

Contact: David Greenberg
John Wiley & Sons, Inc

Dendreon Announces Publication Of Pivotal Phase 3 Study Highlighting Survival Benefit And Safety Profile Of PROVENGE For Advanced Prostate Cancer

2007-04-15T10:35:00.000-07:00

Dendreon Corporation (Nasdaq: DNDN) today announced the publication of the results of its pivotal Phase 3 study (D9901) of PROVENGE(R) (sipuleucel-T) in the July issue of the Journal of Clinical Oncology. The article highlights the significant survival benefit and favorable safety profile of PROVENGE, the Company's investigational active cellular immunotherapy, in men with advanced androgen-independent prostate cancer. The Company plans to submit a Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) later this year to obtain approval to market PROVENGE.

"This trial is an important milestone in the development of new treatments for prostate cancer patients. The survival benefit that was observed has the potential to offer important benefits to patients, and represents the first time an immunotherapy has provided a survival advantage in prostate cancer," said Eric J. Small, M.D., professor of medicine and urology at the University of California, San Francisco and lead author of the publication. "In addition to the observed survival benefit, PROVENGE has a very favorable toxicity and safety profile, with the most common side effects being low grade fevers and chills. A favorable benefit-to-risk profile will be appealing to patients with advanced stage prostate cancer who currently have few appealing treatment options available to them."

The double-blind, placebo-controlled Phase 3 Study D9901 showed that the group of men with asymptomatic, metastatic, androgen-independent prostate cancer who received PROVENGE had a median survival time 4.5 months longer than the median survival seen in the group that had been assigned to receive placebo. For the men who received PROVENGE, there was a 41 percent overall reduction in the risk of death (p-value = 0.010; HR = 1.7). In addition, 34 percent of patients receiving PROVENGE were alive 36 months after treatment compared to 11 percent of patients randomized to receive placebo. These data will form the basis of the Company's BLA to the FDA for marketing approval, which the Company plans to submit later this year.

Patients in the PROVENGE arm had a 31 percent delay in their time to disease progression compared to patients in the placebo arm (p-value = 0.052; HR = 1.45). Furthermore, patients receiving PROVENGE had an approximately 8-fold increase in their T-cell immunity after treatment compared to the placebo group (p < 0.001).

"The survival benefit demonstrated in this trial, combined with the favorable safety profile of PROVENGE, will form the basis for our BLA submission to the FDA later this year," said Mark Frohlich, M.D., vice president of clinical affairs at Dendreon. "We look forward to making this active cellular immunotherapy available for the treatment of the many men with advanced prostate cancer."

The D9901 study was conducted at 19 institutions in the United States and enrolled 127 men with asymptomatic, metastatic androgen-independent (hormone-refractory) prostate cancer. Patients were randomized in a 2:1 ratio to receive three infusions of PROVENGE (n=82) or placebo (n=45) every two weeks for a total of three infusions over a one month period.

Treatment with PROVENGE was generally well tolerated. The majority of side effects were mild, including infusion-related fever and chills that were usually of low grade and typically lasted for one to two days following infusion.

About PROVENGE (sipuleucel-T)

PROVENGE (sipuleucel-T) is an investigational product that may represent the first in a new class of active cellular immunotherapies (ACIs) that are uniquely designed to stimulate a patient's own immune system. ACIs hold promise because they may provide patients with a meaningful survival benefit with low toxicities. PROVENGE targets the prostate cancer antigen, prostatic acid phosphatase (PAP), which is found in approximately 95 percent of prostate cancers. PROVENGE is in late-stage development for the treatment of patients with advanced prostate cancer. In clinical studies, patients typically received three infusions over a one-month period as a complete course of therapy.

About Prostate Cancer

Prostate cancer is the most common non-skin cancer in the United States and the third most common cancer worldwide. More than one million men in the United States have prostate cancer, with an estimated 232,000 new cases of prostate cancer diagnosed each year. More than 30,000 men die each year of the disease.

About Dendreon

Dendreon Corporation is a biotechnology company whose mission is to target cancer and transform lives through the discovery, development and commercialization of novel therapeutics that harness the immune system to fight cancer. The Company uses its experience in antigen identification, antigen engineering and antigen-presenting cell processing to produce active immunotherapy product candidates to potentially stimulate a cell-mediated immune response. PROVENGE (sipuleucel-T) is Dendreon's lead active cellular immunotherapy in Phase 3 development for prostate cancer. The Company also discovered Trp-p8, a cold receptor and transmembrane ion channel in pre-clinical development, which is over-expressed in breast, prostate, lung and colon cancers. For more information about the Company and its programs, visit http://www.dendreon.com.

Except for historical information contained herein, this news release contains forward-looking statements that are subject to risks and uncertainties surrounding the efficacy of PROVENGE to treat men suffering from prostate cancer, risks and uncertainties surrounding the presentation of data to the FDA and approval of product applications by the FDA and risks and uncertainties inherent in the process of discovering, developing and commercializing drugs that are safe and effective for use as human therapeutics. Factors that may cause such differences include risks related to our limited operating history, risks associated with completing our clinical trials, the risk that the safety and/or efficacy results of a clinical trial for PROVENGE will not support an application for a biologics license, the risk that the FDA may interpret data differently than we do or require more data or a more rigorous analysis of data than expected, the risk that the FDA will not approve a product for which a biologics license has been applied, the risk that the results of a clinical trial for PROVENGE or other product may not be indicative of results obtained in a later clinical trial, risks that we may lack the financial resources and access to capital to fund required clinical trials or commercialization of PROVENGE, our dependence on the efforts of third parties, and our dependence on intellectual property. Further information on the factors and risks that could affect Dendreon's business, financial condition and results of operations are contained in Dendreon's public disclosure filings with the U.S. Securities and Exchange Commission, which are available at http://www.sec.gov.

Dendreon Corporation
http://www.dendreon.com/

Study Examines The Use Of A Novel Suprapubic Catheter In Suprapubic Prostatectomy

2007-04-15T09:39:00.001-07:00

UroToday.com - It is well known that in addition to urethral catheter associated discomfort, there is an increased risk of ascending urethral infection, inflammation and stricture formation with urethral catheters. Despite the emergence of a multitude of minimally invasive treatments for BPH, the traditional TURP or suprapubic prostatectomy is still commonly performed. Open prostatectomy offers the advantage of a lower re-treatment rate and more complete removal of the prostate adenoma under direct vision, while it avoids the risk of TUR syndrome.

The post-operative morbidity of the suprapubic prostatectomy includes hemorrhage, clot retention, incontinence, urethral or bladder neck stricture and UTI. Some are related to the use of urethral catheters, such a severe bladder irritation, ascending UTI or epididymoorchitis and urethral stricture formation.

A recent report examines the use of a novel catheter, instead of the traditional urethral catheter, for the post-operative urinary drainage after a suprapubic prostatectomy. The study, by H. Djaladat and colleagues from Tehran Iran, is published in the June 2006 issue of the Journal of Urology.

A total of 146 patients underwent suprapubic prostatectomy for refractory lower urinary tract symptoms or urinary retention. Of the patients, 96 were treated with a novel technique without a urethral catheter but with a specially configured 24 F 3-way suprapubic tube. The tube was placed suprapubically and the end drainage holes were tied off with a silk suture. The balloon was filled within the prostatic fossa after adenoma enucleation and two additional drainage holes were made in the side of the catheter that lies within the bladder to allow for urinary drainage and irrigation. The tube was fixed at the dome of the bladder using a purse string suture to prevent migration. A closed suction drain was placed in the space of Reitzius. Fluid was removed slowly from the novel catheter balloon as the urine cleared. The balloon was completely emptied between 24 and 36 hours and the catheter was removed in 5 to 7 days. The mean balloon fluid volume was 29.5 cc. Post-operative indices were compared between the group using the novel catheter and a group of 48 patients using traditional urethral and suprapubic catheters.

Analysis of the results showed that there was no report of clot retention or significant irritation in the novel catheter group, while 22 (44%) and 19 (38%) in the control group had significant irritative symptoms and at least 1 episode of clot retention. The post-operative decrease in hemoglobin was 0.8 mg/dl in the novel group and 1.9 mg/dl in the control group. There were no reports of epididymoorchitis with the novel catheter but this was identified in 4 (8%) in the control group (p < 0.05). In follow-up at 6 months, all patients underwent cystoscopy. The incidence of membranous urethral strictures was 4.1% in the novel catheter group and 14% in the control group. Four more patients had penile urethral stricture and 3 had bladder neck contractures in the control group. Early incontinence (1 week post-operatively) was also reported in 4% of patients with the novel catheter but in 62% of the control group. It did improve in 95% of patients.

This study suggests improved immediate post-operative morbidity with the use of the novel urinary catheter for use in suprapubic prostatectomy with a decrease in the incidence of urethral stricture disease.

By Michael J. Metro, MD

Reference:
J Urol. 2006 June; 175(6):2083-6
Link Here.
Djaladat H, Mehrsai A, Saraji A, Moosavi S, Djaladat Y, Pourmand G

UroToday - the only urology website with original content written by global urology key opinion leaders actively engaged in clinical practice.

To access the latest urology news releases from UroToday, go to:
http://www.urotoday.com

Copyright © 2006 - UroToday

Intermittent Androgen Deprivation In Biochemical Recurrence Of Prostate Cancer After Radiotherapy

2007-04-15T09:36:00.001-07:00

UroToday.com - Intermittent androgen deprivation (IAD) is commonly used in the treatment of CaP, which theoretically may delay the development of hormone resistance. Dr. Bruchovsky and associates report the outcomes of a Phase II trial using IAD in patients with biochemical recurrence following radiotherapy in the epub version of Cancer.

A group of 103 patients with a PSA of >6ng/ml but no evidence of metastasis were enrolled in the study. They received cyproterone acetate and leuprolide as treatment, with leuprolide given every 4 weeks for up to 8 doses. The leuprolide was then stopped if the PSA level at weeks 24 and 32 was <4.0ng/ml.and resumed when the PSA level was >10ng/ml. Development of androgen independence was defined as 3 sequential increases in the PSA despite castrate levels of serum testosterone.

Mean patient age at study entry was 73 years and mean PSA was 21.2ng/ml. Mean follow-up was 3.7 years. The total number of treatment cycles was 277. The mean time on treatment in cycles 1 and 2 was 36 weeks, which decreased in cycles 3-5. This was because some patients either progressed or reached the end of the study. The average time off treatment was 64 weeks in cycle 1, decreasing 22-27% in cycles 2 -4. Prostate volume decreased in the first 3 cycles (by 40% in cycle 1), but not thereafter.

The main reasons for ending trial participation were end of study in 39%, progression in 24%, and death in 16%. Gleason score had no significant effect on cycle times.

The shortening cycle times are consistent with IAD selecting for patients who have the most androgen-sensitive tumors. This Phase II trial supports that IAD is feasible in this cohort of patients and has few adverse side effects.

By Christopher P. Evans, MD

Reference:
Cancer. 2006 Jun 16; [Epub ahead of print]
Link Here.
Bruchovsky N, Klotz L, Crook J, Malone S, Ludgate C, Morris WJ, Gleave ME, Goldenberg SL

UroToday - the only urology website with original content written by global urology key opinion leaders actively engaged in clinical practice.

To access the latest urology news releases from UroToday, go to:
http://www.urotoday.com

Copyright © 2006 - UroToday

Parameters Associated With Patient Outcomes In Lymph Node Positive Prostate Cancer

2007-04-15T08:40:00.001-07:00

UroToday.com - Dr. Hofer and colleagues report in the June issue of Urology that lymphovascular invasion (LVI) and the nuclear grade of the primary prostate tumor are independent predictors of PSA recurrence in men with lymph node positive CaP.

The retrospective study included 119 eligible men with lymph node positive CaP who underwent radical prostatectomy at the University of Ulm Hospital, Germany. Clinical and pathologic examination was performed.

The mean number of lymph nodes removed was 12 and the mean number positive was 3. Almost 50% of men had only 1 positive node, 22% had 2 and 34% had more than 2 positive nodes. PSA failure occurred n 41% of these men, leaving 59% free of disease with a mean follow-up of 41 months. The 5-year PSA failure-free survival rate was 61% and the mean PSA failure-free survival time was 54 months.

The metastatic growth pattern in the lymph nodes was similar to the architectural growth pattern used for grading the primary tumor. Extra-nodal extension was seen in 55% of the cases, and 25% had lymph nodes with LVI.

Pre-operative PSAS was not predictive of a PSA failure. However, multivariable analysis demonstrated that LVI of the metastasis and nuclear tumor grade were associated with PSA recurrence. These pathologic parameters may help to identify patients at risk for disease recurrence and direct them towards adjuvant therapies and clinical trials.

By Christopher P. Evans, MD

Reference: Urol 2006;67:1016-1021
Link Here.
Hofer MD, Kuefer R, Huang W, Li H, Bismar TA, Perner S, Hautmann RE, Sanda MG, Gschwend JE, Rubin MA

UroToday - the only urology website with original content written by global urology key opinion leaders actively engaged in clinical practice.

To access the latest urology news releases from UroToday, go to:
http://www.urotoday.com

Copyright © 2006 - UroToday

Prostatic Irradiation Doesn't Lead To Any Appreciable Increase In Rectal Cancer Risk

2007-04-15T08:37:00.001-07:00

Men who receive radiation therapy for prostate cancer are not at any appreciable increased risk of developing rectal cancer compared to those not given radiation therapy, according to a new study published in the July 1, 2006, issue of the International Journal of Radiation Oncology*Biology*Physics, the official journal of ASTRO, the American Society for Therapeutic Radiology and Oncology.

This year, 235,000 American men will be diagnosed with prostate cancer. The main ways of dealing with the disease are radiation therapy, surgery and watchful waiting - each of which has its benefits and disadvantages. Researchers have hypothesized that one disadvantage of using radiation to kill the cancer cells in the prostate is that it might also make men more likely to develop cancer in the nearby rectum.

In this study, doctors in Canada evaluated the records of 237,773 men who had prostate cancer. Of them, 33,841 received radiation therapy, 167,607 had their prostate removed surgically and 36,335 received neither treatment. On an initial simple evaluation, doctors found that rectal cancer developed in 243 men who received radiation (0.7 percent), 578 men treated with surgery (0.3 percent), and 227 of the men given neither treatment (0.8 percent). Once doctors had adjusted for the age differences between all the men in the irradiated and non-irradiated groups, they could not find any significant increased risk of rectal cancer in the irradiated men compared to those not given radiation therapy.

"Rectal cancer from other causes is frequent enough in our population to obscure any small incidence of radiation-induced cancer. I hope that the results of this study will help men with prostate cancer and their families put these risks in their proper perspective, and not let their concerns about rectal cancer dissuade them from choosing radiation therapy as a treatment for this disease," said Wayne S. Kendal, M.D., Ph.D., an Associate Professor in Radiation Oncology at the Ottawa Hospital Regional Cancer Centre in Ontario, Canada.

ASTRO (American Society for Therapeutic Radiology and Oncology) is the largest radiation oncology society in the world, with more than 8,500 members who specialize in treating patients with radiation therapies. As the leading organization in radiation oncology, biology and physics, the Society is dedicated to the advancement of the practice of radiation oncology by promoting excellence in patient care, providing opportunities for educational and professional development, promoting research and disseminating research results and representing radiation oncology in a rapidly evolving socioeconomic healthcare environment.

The American Society for Therapeutic Radiology and Oncology
8280 Willow Oaks Corporate Drive, Suite 500
Fairfax, VA 22031
http://www.astro.org
http://www.rtanswers.org

Please plan to join us at ASTRO's upcoming meetings.
* September 8-10, 2006: Translational Research in Radiation Oncology, Physics and Biology - Boston
* September 15-16, 2006: Health Services/Outcomes Research in Oncology - San Diego
* November 5-9, 2006: 48th Annual Scientific Meeting - Philadelphia
Visit here for more information.

Pomegranate Juice Helps Keep PSA Levels Stable In Men With Prostate Cancer, Jonsson Cancer Center Study Finds

2007-04-15T07:36:00.001-07:00

Drinking an eight ounce glass of pomegranate juice daily increased by nearly four times the period during which PSA levels in men treated for prostate cancer remained stable, a three-year UCLA study has found.

The study involved 50 men who had undergone surgery or radiation but quickly experienced increases in prostate-specific antigen or PSA, a biomarker that indicates the presence of cancer. UCLA researchers measured "doubling time," how long it takes for PSA levels to double, a signal that the cancer is progressing, said Dr. Allan Pantuck, an associate professor of urology, a Jonsson Cancer Center researcher and lead author of the study.

Doubling time is crucial in prostate cancer, Pantuck said, because patients who have short doubling times are more likely to die from their cancer. The average doubling time is about 15 months. In the UCLA study, Pantuck and his team observed increases in doubling times from 15 months to 54 months, an almost four-fold increase.

"That's a big increase. I was surprised when I saw such an improvement in PSA numbers," Pantuck said. "In older men 65 to 70 who have been treated for prostate cancer, we can give them pomegranate juice and it may be possible for them to outlive their risk of dying from their cancer. We're hoping we may be able to prevent or delay the need for other therapies usually used in this population such as hormone treatment or chemotherapy, both of which bring with them harmful side effects."

The study appears in the July 1 issue of Clinical Cancer Research, the peer-reviewed journal of the American Association of Cancer Research.

"This is not a cure, but we may be able to change the way prostate cancer grows," Pantuck said. "We don't know yet the specific factors behind this response - that's our next step in this research. We want to find out what cell signaling pathways might be affected, what is happening to keep PSA levels stable."

Pomegranate juice is known to have anti-inflammatory effects and high levels of anti-oxidants, which are believed to protect the body from free-radical damage. It also contains poly-phenols, natural antioxidant compounds found in green tea, as well as isoflavones commonly found in soy, and ellagic acid, which is believed to play a role in cancer cell death.

"There are many substances in pomegranate juice that may be prompting this response," Pantuck said. "We don't know if it's one magic bullet or the combination of everything we know is in this juice. My guess is that it's probably a combination of elements, rather than a single component."

The levels of PSA in men immediately following treatement should be undetectable, Pantuck said. If PSA can be detected, it's an indication of an aggressive cancer that is likely to progress. The men in Pantuck's study all had detectable PSA following treatment. Of the 50 men enrolled, more than 80 percent experienced improvement in doubling times.

Conventional treatment for men with recurrent prostate cancer includes hormonal therapy, a chemical castration which removes testosterone from the system. Men treated with hormonal therapy can experience hot flashes, osteoporosis, fatigue, depression, muscle wasting, loss of libido and erectile dysfunction. If drinking pomegranate juice can delay or prevent the need for hormonal therapy, patients would experience a better quality of life for a longer time, Pantuck said.

The patients in Pantuck's study experienced no side effects and none of the participants had cancers that metastasized during the study.

Pantuck, along with UCLA colleagues including Dr. Arie Belldegrun, professor and chief of urologic oncology, and Dr. David Heber, professor and director of the Center for Human Nutrition, first began research on pomegranate juice in prostate cancer about six years ago, conducting preclinical research in cell cultures and in animals. Those studies showed pomegranate juice slowed the growth of prostate cancer, Pantuck said.

The data was impressive enough to test pomegranate juice in clinical trials, Pantuck said. To confirm their findings, a larger Phase III study, headed up by UCLA, will be conducted at ten centers across the county. UCLA is the only Southern California center involved in the study. For more information on the Phase III trial, call (310) 825-5538.

Pantuck said he has men on the study more than three years out who are not being treated for prostate cancer other than drinking pomegranate juice and their PSA levels continue to be suppressed.

"The juice seems to be working," he said.

The study, performed at the Clark Urology Center, was funded by the Stuart and Linda Resnick Trust. The Resnicks own POM Wonderful, which provided the juice for the study.

UCLA's Jonsson Comprehensive Cancer Center comprises more than 240 researchers and clinicians engaged in research, prevention, detection, control, treatment and education. One of the nation's largest comprehensive cancer centers, the Jonsson center is dedicated to promoting research and translating the results into leading-edge clinical studies. In July 2005, the Jonsson Cancer Center was named the best cancer center in the western United States by U.S. News & World Report, a ranking it has held for six consecutive years.

For more information on the Jonsson Cancer Center, visit our web site at http://www.cancer.mednet.ucla.edu.

UCLA's Jonsson Cancer Center
UCLA Institute for Stem Cell Biology and Medicine

Study Shows Prostate Cancer Vaccine Linked To Longer Survival

2007-04-15T07:33:00.001-07:00

A University of California, San Francisco study has found that men with advanced, often untreatable prostate cancer who received a therapeutic cancer vaccine went on to survive longer than those receiving a placebo.

Study findings showed the vaccine group lived up to an average of four-and-a-half months longer and had a greater than three-fold increase in survival at 36 months when compared to patients in the placebo group.

The study is reported in the July 1, 2006 issue of the Journal of Clinical Oncology.

The double-blind, placebo-controlled phase III clinical trial was conducted to test the efficacy of the vaccine, called sipuleucel-T, in delaying disease progression and prolonging survival in patients with asymptomatic metastatic hormone refractory prostate cancer (HRPC).

Study results showed that the vaccine was well-tolerated by participants. The most common reported adverse effects such as fever and chills were typically mild.

Led by Eric J. Small, MD, UCSF professor of medicine and urology, the study was conducted in collaboration with 19 institutions in the United States and funded by the Dendreon Corporation, a biotechnology company that developed the vaccine.

"This trial is an important milestone in the development of new treatments for prostate cancer patients," said Small. "The potential survival benefit that was observed may offer important benefits to patients and would represent the first time that immunotherapy has provided a survival advantage in prostate cancer."

Sipuleucel-T, known by its product name Provenge, is an investigational immunotherapy vaccine designed to stimulate T-cell immunity to prostatic acid phosphatase, an antigen found in about 95 percent of prostate cancers but not in non-prostate tissue.

A total of 127 patients with asymptomatic metastatic HRPC received three transfusions of sipuleucel-T or placebo every two weeks. Of this group, 115 patients had progressive disease at the time of data analysis and all patients were followed for survival for 36 months.

Prostate cancer is the most common non-skin cancer in the U.S. with more than 200,000 new cases each year. It is the third leading cause of cancer deaths in men after lung and colorectal cancer. Unlike prostate cancer that is detected early, asymptomatic metastatic HRPC is resistant to traditional hormonal therapy, and treatment options have been limited.

The study showed that the median overall survival was 25.9 months for sipuleucel-T-treated patients and 21.4 months for placebo-treated patients. After three years, survival was 34 percent for those treated with the vaccine compared to 11 percent for those taking the placebo.

The clinical trial did not meet its primary endpoint of demonstrating a statistically significant difference in progression of the disease from diagnosis, according to Small.

"We found that the time to disease progression for sipuleucel-T was 11.7 weeks compared to 10.0 weeks for placebo," he said. "This shows the difficulties in using the worsening of the disease as an intermediate marker for overall survival of patients treated with immunotherapy. The study however, suggests that sipueucel-T may provide a survival advantage to asymptomatic HRPC patients."

Many of the phase I and II clinical trials of the vaccine were also undertaken at UCSF and led by Small. He first presented results from the phase III trial at the 2005 meeting of the American Society of Clinical Oncology.

Dendreon Corporation, based in Seattle, Washington, hopes to market the Provenge product commercially in the coming year.

###

Co-authors of the study are Paul F. Schelhammer, Eastern Virginia Medical School, Norfolk, VA; Celestia S. Higano, University of Washington; Charles H. Redfern, Sharp Healthcare, San Diego; John J. Nemunaitis, Mary Crowley Medical Research Center, Dallas; and Frank H. Valone, Suleman S. Verjee, Lori A. Jones and Robert M. Hershberg, Dendreon Corporation.

UCSF is a leading university that consistently defines health care worldwide by conducting advanced biomedical research, educating graduate students in the life sciences, and providing complex patient care.

Contact: Nancy Chan
University of California - San Francisco

Cell Genesys Announces Publication Of Encouraging Phase 1/2 Clinical Results For GVAX(R) Immunotherapy For Prostate Cancer In Early Stage Patients

2007-04-15T06:37:00.001-07:00

Cell Genesys, Inc. (Nasdaq: CEGE) today announced that the results from an initial clinical trial of GVAX(R) immunotherapy for prostate cancer in patients with early-stage disease have been published in a June issue of Clinical Cancer Research by a team led by Jonathan Simons, M.D., professor of Hematology and Oncology, Winship Cancer Institute, Emory University School of Medicine. The Phase 1/2 trial enrolled 21 patients with rising prostate specific antigen (PSA) levels following prostatectomy and who had not received any other treatment for their prostate cancer, including hormone therapy. The results showed that 16 of 21 (76%) patients showed a statistically significant decrease in the rate of rise of PSA (PSA slope) post-treatment compared with the remaining five patients (p<0.001). One patient had a partial PSA response (>50% reduction of PSA) of 7-month duration. GVAX cancer immunotherapy was generally well tolerated, with self-limited injection site reactions, and mild flu-like symptoms being the most frequently reported side effects. In addition to clinical activity, the publication reported immunologic findings confirming that GVAX immunotherapy for prostate cancer resulted in the induction of immune responses as evidenced by the formation of antibodies directed against prostate cancer cells.

Cell Genesys has completed five Phase 1 and Phase 2 clinical trials of GVAX immunotherapy for prostate cancer in approximately 200 patients with various stages of recurrent prostate cancer, and each trial has demonstrated a favorable safety profile. The initial Phase 1 /2 clinical trial in early- stage prostate cancer described in the above publication was conducted at Johns Hopkins Oncology Center. GVAX immunotherapy treatment was administered at a fixed dose in eight weekly intradermal injections in an outpatient setting. As noted above, one patient had a partial PSA response of 7-month duration which was associated with a corresponding decline in the tumor- associated marker, carcinoembryonic antigen (CEA), as well as induction of a high titer antibody response against a prostate cancer antigen. The titer of this antibody decreased when treatment ended, and subsequent tumor progression based on a rising PSA occurred. In addition, several candidate tumor- associated antigens recognized by treatment-induced antibodies were identified in the study, including antigens reported to be involved in modulation of immune response and cancer metastases.

"While our Phase 3 clinical trials and registration strategy for GVAX immunotherapy for prostate cancer are currently focused on the treatment of advanced prostate cancer, we are pleased to also obtain these encouraging results in an earlier-stage of the disease," said Joseph J. Vallner, Ph.D., president and chief operating officer of Cell Genesys. "We believe that GVAX immunotherapy for prostate cancer may have potential for the treatment of prostate cancer at various stages of the disease and we look forward to initiation of future label-expansion studies."

GVAX immunotherapy for prostate cancer is currently being studied in two Phase 3 clinical trials expected to enroll approximately 1200 patients with metastatic hormone-refractory prostate cancer (HRPC), comprising one of the largest Phase 3 clinical programs ever conducted in men with advanced prostate cancer. The first trial (VITAL-1) is enrolling chemotherapy naпve, asymptomatic patients without cancer-related pain and will compare GVAX cancer immunotherapy to Taxotere chemotherapy plus prednisone. The second trial (VITAL-2) is enrolling patients who are symptomatic with cancer-related pain and will compare GVAX cancer immunotherapy plus Taxotere to Taxotere plus prednisone. Each Phase 3 trial is expected to enroll 600 patients and is designed to demonstrate a survival benefit compared to Taxotere plus prednisone. Cell Genesys received Special Protocol Assessments (SPA) from the FDA for each of the VITAL-1 and VITAL-2 Phase 3 studies as well as Fast Track Status for the product itself.

The company's ongoing Phase 3 program is supported by the median survival results from two, independent, multi-center Phase 2 clinical trials in approximately 115 patients that are not only consistent with each other, but also compare favorably to the previously published median survival of 18.9 months for metastatic HRPC patients treated with Taxotere(R) (docetaxel) chemotherapy plus prednisone, the current standard of care. The Phase 3 program is designed to confirm this potential survival benefit for GVAX immunotherapy for prostate cancer.

Cell Genesys' GVAX cancer immunotherapies are whole-cell products which are designed to present the immune system with a broad spectrum of tumor antigens and stimulate an immune response against the patient's tumor. GVAX immunotherapy for prostate cancer is comprised of two prostate cancer cell lines that have been modified to secrete GM-CSF (granulocyte-macrophage colony stimulating factor), an immune stimulatory hormone which plays a key role in stimulating the body's immune response, and then irradiated for safety. GVAX cancer immunotherapy for prostate cancer is being developed as a non patient- specific, "off-the-shelf" pharmaceutical product.

Cell Genesys is focused on the development and commercialization of novel biological therapies for patients with cancer. The company is currently pursuing two clinical stage product platforms -- GVAX(R) cancer immunotherapies and oncolytic virus therapies. Ongoing clinical trials include Phase 3 trials of GVAX immunotherapy for prostate cancer, Phase 2 trials of GVAX immunotherapy for pancreatic cancer and leukemia, and a Phase 1 trial of CG0070 oncolytic virus therapy for bladder cancer. Cell Genesys continues to hold an equity interest in its former subsidiary, Ceregene, Inc., which is developing gene therapies for neurodegenerative disorders. Cell Genesys is headquartered in South San Francisco, CA and has its principal manufacturing operation in Hayward, CA. For additional information, please visit the company's website at http://www.cellgenesys.com.

Statements made herein about the company, other than statements of historical fact, including statements about the company's progress, results and timing of clinical trials and preclinical programs and the nature of product pipelines are forward-looking statements and are subject to a number of uncertainties that could cause actual results to differ materially from the statements made, including risks associated with the success of clinical trials and research and development programs, the regulatory approval process for clinical trials, competitive technologies and products, patents, continuation of corporate partnerships and the need for additional financings. For information about these and other risks which may affect Cell Genesys, please see the company's Annual Report on Form 10-K for the year ended December 31, 2005 filed on March 13, 2006 as well as Cell Genesys' reports on Form 10-Q and 8-K and other reports filed from time to time with the Securities and Exchange Commission. The company assumes no obligation to update the forward-looking information in this press release.

Cell Genesys, Inc.
http://www.cellgenesys.com

Prostatic Irradiation Doesn't Lead To Any Appreciable Increase In Rectal Cancer Risk

2007-04-15T06:34:00.001-07:00

Men who receive radiation therapy for prostate cancer are not at any appreciable increased risk of developing rectal cancer compared to those not given radiation therapy, according to a new study published in the July 1, 2006, issue of the International Journal of Radiation Oncology*Biology*Physics, the official journal of ASTRO, the American Society for Therapeutic Radiology and Oncology.

This year, 235,000 American men will be diagnosed with prostate cancer. The main ways of dealing with the disease are radiation therapy, surgery and watchful waiting пїЅ each of which has its benefits and disadvantages. Researchers have hypothesized that one disadvantage of using radiation to kill the cancer cells in the prostate is that it might also make men more likely to develop cancer in the nearby rectum.

In this study, doctors in Canada evaluated the records of 237,773 men who had prostate cancer. Of them, 33,841 received radiation therapy, 167,607 had their prostate removed surgically and 36,335 received neither treatment. On an initial simple evaluation, doctors found that rectal cancer developed in 243 men who received radiation (0.7 percent), 578 men treated with surgery (0.3 percent), and 227 of the men given neither treatment (0.8 percent). Once doctors had adjusted for the age differences between all the men in the irradiated and non-irradiated groups, they could not find any significant increased risk of rectal cancer in the irradiated men compared to those not given radiation therapy.

"Rectal cancer from other causes is frequent enough in our population to obscure any small incidence of radiation-induced cancer. I hope that the results of this study will help men with prostate cancer and their families put these risks in their proper perspective, and not let their concerns about rectal cancer dissuade them from choosing radiation therapy as a treatment for this disease," said Wayne S. Kendal, M.D., Ph.D., an Associate Professor in Radiation Oncology at the Ottawa Hospital Regional Cancer Centre in Ontario, Canada.

###

For more information on radiation therapy for prostate cancer, please visit http://www.rtanswers.org/.

ASTRO is the largest radiation oncology society in the world, with more than 8,500 members who specialize in treating patients with radiation therapies. As the leading organization in radiation oncology, biology and physics, the Society is dedicated to the advancement of the practice of radiation oncology by promoting excellence in patient care, providing opportunities for educational and professional development, promoting research and disseminating research results and representing radiation oncology in a rapidly evolving socioeconomic healthcare environment.

Contact: Beth Bukata
American Society for Therapeutic Radiology and Oncology

In A Phase III Lipid Interim Analysis, ACAPODENE Treatment Lowered Cholesterol And Raised HDL In Prostate Cancer Patients On Androgen Deprivation

2007-03-07T08:40:00.001-08:00

New Test Detects Prostate Cancer Spread At The Earliest Time

2007-03-07T08:36:00.001-08:00

Urologist Plays Key Role In Determining Use Of Hormone Therapy In Prostate Cancer

2007-03-07T07:41:00.001-08:00

Dutasteride Induces Apoptosis In Androgen Sensitive Prostate Cancer Cell Lines

2007-03-07T07:36:00.001-08:00

High Surgeon Radical Prostatectomy Volume Is Linked To Lower Hospital Charges

2007-03-07T06:38:00.001-08:00

Shift In Prostate Cancer Gleason Grades From 1989 To 2001

2007-03-07T06:35:00.001-08:00

Obesity Undermines Radiation Treatment For Prostate Cancer

2007-03-07T05:39:00.001-08:00

Obesity In Prostate Cancer Patients Predicts Cancer Recurrence And Progression

2007-03-07T05:35:00.001-08:00

For Men With Prostate Cancer, Treatment Information Fails To Address Fears

2007-03-07T04:39:00.001-08:00

Breast Cancer Drug To Extend Lives Of Men With Late Stage Prostate Cancer

2007-03-07T04:35:00.001-08:00

Obesity Is Associated With Less Favorable Outcome After Radiation Therapy For Prostate Cancer

2007-03-07T03:39:00.001-08:00

Dendreon Announces Publication Of Pivotal Phase 3 Study Highlighting Survival Benefit And Safety Profile Of PROVENGE For Advanced Prostate Cancer

2007-03-07T03:35:00.001-08:00

Study Examines The Use Of A Novel Suprapubic Catheter In Suprapubic Prostatectomy

2007-03-07T02:42:00.001-08:00