Phase I Sudy Combining Gefitinib With Docetaxel And Estramustine Reported

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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