Phase II trial of 96-hour paclitaxel plus oral estramustine phosphate in metastatic hormone-refractory prostate cancer

Purpose: To evaluate the antitumor activity of 96-hour paclitaxel and daily oral estramustine phosphate (EMP) in patients with metastatic hormone-refractory prostate cancer (HRPC). Patients and Methods: Thirty-four patients with adenocarcinoma of the prostate that progressed after one or more hormonal therapies and a trial of antiandrogen withdrawal were enrolled onto this phase II trial. patients received paclitaxel 120 mg/m(2) by 96-hour intravenous (IV) infusion on days 1 through 4 of each 21-day cycle, together with daily oral EMP 600 mg/m(2)/d, continuously. Results: Four of nine patients with measurable disease objective responses (one complete response [CR] and three partial responses [PRs]) in liver (two patients) or nodes (two patients) of 2, 6, 8, and 20 months' duration. Of 25 assessable patients with metastases limited to bone, 14 had a greater than or equal to 50% decline in pretreatment prostate-specific antigen (PSA) level sustain 6 weeks and seven had a greater than or equal to 80% decline. Overall, 17 of 32 patients (53.1%) with elevated pretreatment PSA levels had a greater than or equal to 50% decline of PSA and nine (28.1%) had a greater than or equal to 80% decrease. The main toxicities (greater than or equal to grade 2) were nausea, fluid retention, and fatigue, which occurred in 33%, 33%, and 24.2% of patients. Median time to progression, based on increasing PSA level and other clinical criteria, was 22.5 weeks. The estimated median overall survival time is 69 weeks. Conclusion: The combination of EMP and 96-hour paclitaxel an active regimen for patients with HRPC. These results further support the therapeutic strategy of combining agents that impair microtubule function by complementary mechanisms. (C) 1991 by American Society of Clinical Oncology.