PHASE-II STUDY OF ESTRAMUSTINE, ORAL ETOPOSIDE, AND VINORELBINE IN HORMONE-REFRACTORY PROSTATE-CANCER

Hormone-refractory prostate cancer is characterized by a low response rate following second-line therapy. Encouraging results have been repo rted in Phase II studies with estramustine associated with vinblastine or etoposide. Vinorelbine is a new semisynthetic vinca alkaloid that has demonstrated activity in prostate cancer. We therefore evaluated t he activity of the following schedule: estramustine, 400 mg/m(2) orall y days 1-42; etoposide, 50 mg/m(2) orally days 1-14; and 28-42; vinore lbine, 20 mg/m(2) days 1, 8, 28, and 35; cycles being repeated every 8 weeks. Twenty-five patients have been included and are assessable for response and side effects. Patient characteristics were as follows: m edian age, 71 years (range 55-81); ECOG performance status 0-2; nonoss eous disease, 3 cases; bone metastases, 23 cases. Sixty-two cycles hav e been delivered. Two patients with measurable disease and six patient s with bone disease had a partial remission for an overall response ra te of 32% (95% confidence interval 15-53%). Seven patients had stabili zation of disease and 10 had progression of disease. Median duration o f response was 3 months (range 2-5). Prostate-specific antigen in 14 p atients (56%) decreased from baseline by at least 50%. Toxicity was ma nageable. Neutropenia was mild, with only three cases of grade III-IV toxicity. Two patients had severe anemia. The results of this study in dicate that the schedule is active and well tolerated in hormone-refra ctory prostate cancer patients.