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Ixabepilone (Epothilone B Analogue BMS-247550) Is Active in Chemotherapy-Naive Patients With Hormone-Refractory Prostate Cancer: A Southwest Oncology Group Trial S0111

From the University of Michigan Comprehensive Cancer Center, Ann Arbor; Karmanos Cancer Institute, Wayne State University, Detroit, MI; Southwest Oncology Group Statistical Center, Seattle, WA; University of California at Davis, Cancer Center, Sacramento, CA; Columbia University, New York, NY; National Cancer Institute, Bethesda, MD; and University of Colorado, Denver, CO

Address reprint requests to Southwest Oncology Group (SWOG-S0111) Operations Office, 14980 Omicron Dr, San Antonio, TX 78245-3217; e-mail: mahahuss{at}med.umich.edu

PURPOSE: The epothilones are a new class of tubulin-polymerizing agents with activity in taxane-sensitive and resistant tumor models. We evaluated ixabepilone (BMS-247550) in patients with metastatic hormone-refractory prostate cancer (HRPC).

METHODS: Eligible patients had chemotherapy-naive metastatic HRPC, a Zubrod performance status of 0 to 2, and adequate organ function. All patients received BMS-247550 at 40 mg/m² over 3 hours every 3 weeks. The primary end point was proportion of patients achieving a prostate-specific antigen (PSA) response.

RESULTS: Forty-eight patients with metastatic HRPC were registered. Forty-two patients were eligible, with a median age of 73 years and a median PSA level of 111 ng/mL; 78% had bone-only or bone and soft tissue metastases, and 88% had objective radiologic disease progression at registration. Grade 3 and 4 adverse events (AEs) occurred in 16 and three patients, respectively. All grade 4 toxicities were neutropenia or leukopenia. The most frequent grade 3 AEs were neuropathy (eight patients), hematologic toxicity (seven patients), flu-like symptoms, and infection (five patients each). There were no grade 3/4 thrombocytopenia or grade 5 AEs. There were 14 confirmed PSA responses (33%; 95% CI, 20% to 50%); 72% of PSA responders had declines greater than 80%, and two patients achieved an undetectable PSA. The estimated median progression-free survival is 6 months (95% CI, 4 to 8 months), and the median survival is 18 months (95% CI, 13 to 24 months).

CONCLUSION: Ixabepilone has demonstrated activity in patients with chemotherapy-naive metastatic HRPC. Major toxicities were neutropenia and neuropathy. Further testing to define its activity relative to standard therapy is warranted.

Supported in part by the following United States Public Health Service Cooperative Agreement Grants No. awarded by the National Cancer Institute, Department of Health and Human Services: CA38926, CA32102, CA27057, CA46441, CA14028, CA68183, CA42777, CA12644, CA58861, CA63845, CA20319, CA45450, CA45560, CA74647, CA35178, and CA67663.

Presented in part at the Prostate Cancer Oral Session of the 40th Annual Meeting of the American Society of Clinical Oncology, June 5-8, 2004, New Orleans, LA.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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