OBJECTIVE: We evaluated efficacy and toxicity of weekly paclitaxel in metastatic hormone-refractory prostate cancer (HRPC). MATERIALS AND METHODS: Patients received weekly paclitaxel 80 mg/m2 by 1-hour intravenous infusion. A course of therapy consisted of 6 weekly treatments and 2 weeks rest. PSA response was defined as a PSA decrease not less than 50%, maintained for 4 weeks with stable or improved performance status. RESULTS: The study enrolled 43 patients with metastatic HRPC diagnosed a median of 10.5 months before. Median age was 69 years (range, 58-86 years). Five had previous radioisotopes treatment for bone pain, 15 had previous treatment of metastatic hormone-refractory disease, mainly estramustine. The median number of weeks of therapy delivered each patient was 8 (range, 1-24 weeks; cumulative, 369 weeks). PSA response was registered in 13 patients of 36 evaluable for PSA response (36.1%; 95% confidence interval [CI], 20.8-53.8), with a median duration of 4.2 months. Among 16 patients evaluable for objective response, 5 partial responses (31.2%; 95% CI, 11.0-58.7) and 9 stable diseases were registered. Eleven (42.3%) of 26 patients presenting with cancer-related symptoms had improvement. Median survival time was 12.8 months (95% CI, 10.1-15.5) Therapy was associated with acceptable hematological toxicity (anemia grade 3, 16%; neutropenia grade 3-4, 12%) and moderate nonhematologic toxicities (thrombosis/embolism 10%; fatigue all grades, 60%). CONCLUSION: Docetaxel every 3 weeks is the standard of care for metastatic HRPC, but our results suggest some activity and an acceptable toxicity of weekly paclitaxel.