Weekly 1-hour infusion of paclitaxel: Clinical feasibility and efficacy in patients with hormone-refractory prostate carcinoma

BACKGROUND. Preclinically, paclitaxel given according to an intense bolus schedule has significant antitumor activity against human prostate carcinoma cell lines in SCID mice. The authors evaluated the feasibility and efficacy of weekly 1-hour infusion of paclitaxel in patients with metastatic hormone-refractory prostate carcinoma (HRPC). METHODS. A total of 18 patients with progressive metastatic HRPC were enrolled. Patients had to have no prior chemotherapy. Paclitaxel was infused weekly at a dose of 150 mg/m² over 1 hour for 6 weeks every 8 weeks. RESULTS. Eighteen patients with a median age of 68.5 years and a median prostate specific antigen (PSA) level of 82 ng/mL (range, 2.17-3196 ng/mL) were enrolled. The median number of prior hormone treatments was 2, and 12 patients on antiandrogens completed antiandrogen withdrawal. Ten of eighteen patients had bone-only metastasis and eight had metastasis to bone with lymph node and/or visceral metastasis. Seventeen patients received a total of 31 cycles (157 courses) and 1 patient refused chemotherapy. All patients were included in response evaluation. Of the 18 patients with measurable disease, 4 achieved a major response, with 1 complete response (in the lung) and 3 partial responses (1 in the liver and 2 in the lymph nodes). Seven of eighteen patients (39%) had a PSA decline of ≥50%. The major high grade toxicity was peripheral neuropathy, with 6 patients (35%) developing Grade 3 toxicity. CONCLUSIONS. Weekly 1-hour paclitaxel has activity in patients with HRPC. The major toxicity is peripheral neuropathy. The minimal myelosuppressive effects make a modified schedule (lower doses on the same schedule or a shorter schedule of the same dose) attractive for future combination chemotherapy trials. (C) 2000 American Cancer Society.