Phase II trial of oral estramustine, oral etoposide, and intravenous paclitaxel in hormone-refractory prostate cancer

Purpose: To evaluate the combination of intravenous (IV) paclitaxel, oral e stramustine, and oral etoposide in patients with advanced hormone-refractor y prostate cancer. Patients and Methods: Forty patients wish carcinoma of the prostate that wa s progressing despite hormonal therapy and who had undergone antiandrogen w ithdrawal (if previously treated with an antiandrogen) were enrolled onto t his phase II trial. Patients were treated with oral estramustine 280 mg tid and oral etoposide 100 mg/d for 7 days, with paclitaxel 135 mg/m(2) IV ove r 1 hour on day 2 of each 21-day treatment cycle. Patients received a maxim um of six cycles of therapy. Results: Thirty-seven patients were assessable for response; Twenty-two had measurable disease at baseline; response was not assessable in six of thes e patients. Overall response was 45% (10 of 22 patients; 95% confidence int erval [CI], 24% to 68%), and response was 63% (10 of 16) in assessable pati ents. Twenty-six patients had a greater than or equal to 50% decrease from their baseline prostate-specific antigen levels during therapy for a respon se rate of 65% (95% CI, 48% to 79%) by this criterion. Median duration of r esponse was 3.2 months, with an estimated median survival of 12.8 months. M ajor toxicities of therapy were leukopenia (eight patients had greater than or equal to grade 4 leukopenia) and anemia. Hematologic toxicity seemed to be associated with liver metastases. Serial measurements in 24 patients us ing the functional Assessment of Cancer Therapy-Prostate (FACT-P) showed no significant change in qualify of life (QOL) as a result of therapy. Conclusion: The combination of IV paclitaxel, oral estramustine, and oral e toposide is active in patients with advanced prostate cancer. The regimen i s tolerable and does not have a significant impact on QOL as measured by th e FACT-P in a limited sample of patients. (C) 1999 by American Society of C linical Oncology.