Paclitaxel, estramustine and carboplatin combination chemotherapy after initial docetaxel-based chemotherapy in castration-resistant prostate cancer

Objectives: Management of castration-resistant prostate cancer after docetaxel has become an unmet need for which various agents have been investigated. We report our experience with a paclitaxel-based regimen. Methods: From February 2004 to November 2007, 15 patients (PTS) received paclitaxel 80 mg/m² weekly on day 1, carboplatin (AUC = 6) on day 1 every 21 days and estramustine 140 mg on days -1, 0 and 1 every week. Results: Patient characteristics are: median age 67 years (range 44-81), median performance status (Eastern Cooperative Oncology Group) 1 (range 0-2) and median prostate-specific antigen 67.5 ng/ml (range 1.5-480). All PTS had soft-tissue and 12 (80%) also had osseous disease. A >50% decrease in prostate-specific antigen levels occurred in 9 PTS (60%, 95% CI 32-84). Responses included a partial response in 6 (40%, 95% CI 16-68) and stable disease in 5 PTS (33%). Median duration of progression-free survival was 4.0 months (range 1.1-13) and median survival was 14.6 months. After a median of 4 cycles (range 1-7), significant toxicity included fatigue grade 3 in 2 PTS (13%), neuropathy grade 2 and grade 4 in 1 patient each, and a single episode of grade 3 edema. Myelosuppression was mild. Two PTS (13%) had urinary tract infection and 1 patient neutropenic fever. One patient died due to brain hemorrhage. Conclusions: Administration of second-line paclitaxel-based chemotherapy after docetaxel therapy is active in PTS with castration-resistant prostate cancer. This regimen is too toxic for palliative therapy. Careful patient selection is needed when this regimen is considered for therapy in these PTS.