Chemotherapy Combination Shows Efficacy in Hormone-Refractory Prostate Cancer

Docetaxel (Taxotere) combined with estramustine phosphate (Emcyt) and low-dose hydrocortisone appears to be a promising treatment for men with hormone-refractory prostate cancer, according to the results of a phase II trial conducted by the Cancer and Leukemia Group B (CALGB) and presented at the 1999 meeting of the American Society of Clinical Oncology (ASCO). The study, funded by the National Cancer Institute (NCI), found that the combination treatment was effective and well tolerated.

“When hormone therapy is no longer successful in men with prostate cancer, chemotherapy may be tried,” said Diane Savarese, md, of the University of Massachusetts. “However, current drug therapy, particularly single-agent therapy, confers limited benefit, and the development of new agents and combinations of agents may ultimately prove to be the most effective treatment once hormone resistance has emerged. Indeed, our data suggest that the docetaxel/estramustine combination may represent an encouraging approach.”

The study enrolled 47 men with an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 whose prostate cancer had progressed after initial hormone therapy. Patients who had undergone prior chemotherapy or who had a history of thrombotic events or severe cardiovascular disease were ineligible for the study.

Participants received intravenous docetaxel, 70 mg/m² on the second day of every 3-week cycle; oral estramustine, 10 mg/kg/d in divided doses for 5 days; and oral hydrocortisone, 40 mg/d.

Study Results

Overall, 40 patients were evaluable for response and/or toxicity. Of the 39 men with initially elevated prostate-specific antigen (PSA ) levels, 27 (69%) had a greater than 50% decline in PSA. Of these patients, 21 had a greater than 75% decrease.

Measurable soft-tissue disease was present in 21 of 40 patients who received at least two cycles of therapy. Of these patients, one had a complete response after six cycles, and three had a partial response in soft tissue.

Side effects of the combnation treatment included modest hematologic toxicity. Gastrointestinal disturbances and nonhematologic toxicity occurred infrequently.

Based on the favorable results of this study, phase III trials should be undertaken to compare the combination regimen with other drugs that have shown activity in patients with hormone-refractory prostate cancer. including mitoxantrone (Novantrone) and hydrocortisone, said Dr. Savarese.