Objectives. The efficacy of weekly high-dose paclitaxel in androgen-independent prostate carcinoma and its cytotoxic synergy with estramustine led to the evaluation of a weekly schedule of paclitaxel and estramustine in this Phase II trial. Methods. Patients were eligible if they had metastatic prostate adenocarcinoma with objective progression or rising prostate-specific antigen (PSA) levels despite androgen deprivation therapy and antiandrogen withdrawal. Prior radiation and/or one prior chemotherapy regimen was permitted. A Zubrod performance status of 2 or less and adequate bone marrow and hepatic and renal function were required. Estramustine was administered orally at a dose of 280 mg three times daily on days 1 to 3, 8 to 10, and 15 to 17. Paclitaxel (150 mg/m2) was administered as a 1-hour intravenous infusion on days 2, 9, and 16. Therapy was repeated every 28 days (one cycle). Results. Twenty-eight patients were enrolled (median age 71.5 years). Fifteen patients had measurable disease (nine nodal and seven visceral) and 13 had bone-only metastases. A total of 116 cycles of therapy were delivered (median 4 cycles per patient, range 1 to 12). Nine patients required dose reduction. The predominant toxicities consisted of grade 3 neuropathy in 6 patients and grade 3 and 4 neutropenia in 4 patients, with one hospitalization for febrile neutropenia. Three patients had thrombotic manifestations: one deep venous thrombosis and two non-Q wave myocardial infarctions. Of the 28 patients, 26 were assessable for response. Of 13 patients with measurable disease, 5 demonstrated a partial response (1 in the liver and 4 in the lymph nodes), and 8 of 13 patients with bone-only metastases had a 50% or greater decrease in PSA level. Three patients had a 90% or greater decline in PSA. The overall PSA response rate was 61.53% (95% confidence interval 38.1% to 74.2%). The median time to progression was 4.64 months, and the median survival was 13 months. Conclusions. The combination of weekly estramustine and paclitaxel is active in metastatic androgen-independent prostate cancer.
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