PHASE-II TRIAL OF 96-HOUR PACLITAXEL PLUS ORAL ESTRAMUSTINE PHOSPHATEIN 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 ho rmone-refractory prostate cancer (HRPC). Patients and Methods: Thirty- four patients with adenocarcinoma of the prostate that progressed afte r one or more hormonal therapies and a trial of antiandrogen withdrawa l 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, cont inuously. Results: Four of nine patients with measurable disease objec tive responses (one complete response [CR] and three partial responses [PRs]) in liver (two patients) or nodes (two patients) of 2, 6, 8, an d 20 months' duration. Of 25 assessable patients with metastases limit ed to bone, 14 had a greater than or equal to 50% decline in pretreatm ent prostate-specific antigen (PSA) level sustain 6 weeks and seven ha d 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 equ al 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 increas ing PSA level and other clinical criteria, was 22.5 weeks. The estimat ed median overall survival time is 69 weeks. Conclusion: The combinati on of EMP and 96-hour paclitaxel an active regimen for patients with H RPC. These results further support the therapeutic strategy of combini ng agents that impair microtubule function by complementary mechanisms . (C) 1991 by American Society of Clinical Oncology.