ASCODocetaxel (Taxotere) plus estramustine(Drug information on estramustine) phosphate (Emcyt) and low-dose hydrocortisone(Drug information on hydrocortisone) proved effective and well tolerated in a phase II study of men with hormone-refractory prostate cancer. The study was conducted by the Cancer and Leukemia Group B (CALGB) and presented at the ASCO annual meeting.
When hormone therapy is no longer successful in men with prostate cancer, chemotherapy may be tried, Diane Savarese, MD, of the University of Massachusetts, said at a poster session. However, current drug therapy, particularly single-agent therapy, confers limited benefit, and the development of new agents and combinations may ultimately prove to be the most effective treatment once hormone resistance has emerged. Indeed, our data suggest that the docetaxel(Drug information on docetaxel)/estramustine combination may represent an encouraging approach.
The study included 47 men with ECOG performance status of 0 to 2 whose prostate cancer had progressed after initial hormone therapy. Patients who had received prior chemotherapy or who had a history of thrombotic events or severe cardiovascular disease were not eligible.
The patients received intravenous docetaxel, 70 mg/m², on day 2 of an every-3-week cycle; oral estramustine, 10 mg/kg/day, in divided doses for 5 days; and oral hydrocortisone, 40 mg/day. Forty patients were evaluable for response and/or toxicity.
Decline in PSA Levels
Of the 39 men with initially elevated PSA levels, 27 (69%) had a greater than 50% decline in PSA, Dr. Savarese said. Of these 27 men, 21 had a greater than 75% decline. Of 40 patients who received at least two cycles of therapy, 21 had measurable soft tissue disease. Of these patients, one had a complete response after six cycles, and three had a partial response.
Side effects included modest hematologic toxicity, Dr. Savarese said. Nonhe-matologic toxicity and gastrointestinal disturbances were infrequent.
Based on these favorable results, Dr. Savarese and her colleagues said that phase III studies should be undertaken to compare the docetaxel/estramustine combination regimen with other agents that have been shown to have activity in hormone-refractory prostate cancer such as mitoxantrone(Drug information on mitoxantrone) (Novantrone).