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/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 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 8 [corrected] 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. Copyright 2000 American Cancer Society.