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 s chedule has significant antitumor activity against human prostate carcinoma cell lines in SCID mice. The authors evaluated the feasibility and efficac y of weekly 1-hour infusion of paclitaxel in patients with metastatic hormo ne-refractory prostate carcinoma (HRPC). METHODS. A total of 18 patients with progressive metastatic HRPC were enrol led. Patients had to have no prior chemotherapy. Paclitaxel was infused wee kly at a dose of 150 mg/m(2) over 1 hour for 6 weeks every 8 weeks. RESULTS. Eighteen patients with a median age of 68.5 years and a median pro state specific antigen (PSA) level of 82 ng/mL (range, 2.17-3196 ng/mL) wer e enrolled. The median number of prior hormone treatments was 2, and 12 pat ients on antiandrogens completed antiandrogen withdrawal. Ten of eighteen p atients had bone-only metastasis and eight had metastasis to bone with lymp h node and/or visceral metastasis. Seventeen patients received a total of 3 1 cycles (157 courses) and 1 patient refused chemotherapy. All patients wer e included in response evaluation. Of the 18 patients with measurable disea se, 4 achieved a major response, with 1 complete response tin the lung) and 3 partial responses (1 in the liver and 2 in the lymph nodes). Seven of ei ghteen patients (39%) had a PSA decline of greater than or equal to 50%. Th e 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. T he major toxicity is peripheral neuropathy. The minimal myelosuppressive ef fects make a modified schedule (lower doses on the same schedule or a short er schedule of the same dose) attractive for future combination chemotherap y trials. (C) 2000 American Cancer Society.