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Multi-Institutional Randomized Phase II Trial of the Epothilone B Analog Ixabepilone (BMS-247550) With or Without Estramustine Phosphate in Patients With Progressive Castrate Metastatic Prostate Cancer

From the Genitourinary Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Department of Nursing, Memorial Sloan-Kettering Cancer Center and Department of Medicine, Joan and Sanford I. Weill Medical College of Cornell University, New York, NY; University of California, San Francisco, CA; Dana-Farber Partners Cancer Care, Boston, MA; The University of Texas M.D. Anderson Cancer Center, Houston, TX; University of Michigan, Ann Arbor, MI; National Cancer Institute, Bethesda, MD

Address reprint requests to Matthew D. Galsky, MD, Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10021; e-mail: galskym{at}mskcc.org

PURPOSE: To evaluate the antitumor activity and safety of the epothilone B analog, ixabepilone, with or without estramustine phosphate (EMP), in chemotherapy-naive patients with progressive castrate metastatic prostate cancer.

PATIENTS AND METHODS: Patients were randomly assigned to receive ixabepilone (35 mg/m²) by intravenous infusion every 3 weeks with or without EMP 280 mg orally three times daily on days 1 to 5.

RESULTS: Between December 2001 and October 2003, 92 patients were enrolled and randomly assigned to treatment with ixabepilone alone (45 patients) or in combination with EMP (47 patients). Grades 3 and 4 toxicities experienced by more than 5% of patients included neutropenia (22%), fatigue (9%), and neuropathy (13%) on the ixabepilone arm, and neutropenia (29%), febrile neutropenia (9%), fatigue (9%), neuropathy (7%), and thrombosis (6%) on the ixabepilone + EMP arm. Post-treatment declines in prostate-specific antigen of 50% were achieved in 21 of 44 patients (48%; 95% CI, 33% to 64%) on the ixabepilone arm, and 31 of 45 patients (69%; 95% CI, 55% to 82%) on the ixabepilone + EMP arm. In patients with measurable disease, partial responses were observed in eight of 25 patients (32%; 95% CI, 14% to 50%) on the ixabepilone arm, and 11 of 23 (48%; 95% CI, 27% to 68%) on the ixabepilone + EMP arm. Time to prostate-specific antigen progression was 4.4 months (95% CI, 3.1 to 6.9 months) on the ixabepilone-alone arm and 5.2 months (95% CI, 4.5 to 6.8 months) on the combination arm.

CONCLUSION: Ixabepilone, with or without estramustine phosphate, is well tolerated and has antitumor activity in patients with castrate metastatic prostate cancer.

Supported in part by a grant from the Cancer Therapy Evaluation Program NIH-CM17105, Prostate Cancer Foundation, and PepsiCo Foundation.

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

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

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