Originally published as JCO Early Release 10.1200/JCO.2006.08.9102 on July 2 2007

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Phase II Clinical Trial of Ixabepilone (BMS-247550), an Epothilone B Analog, in Patients With Taxane-Resistant Metastatic Breast Cancer

Eva Thomas, Josep Tabernero, Monica Fornier, Pierfranco Conté, Pierre Fumoleau, Ana Lluch, Linda T. Vahdat, Craig A. Bunnell, Howard A. Burris, Patrice Viens, José Baselga, Edgardo Rivera, Valentina Guarneri, Valerie Poulart, Judith Klimovsky, David Lebwohl, Miguel Martin

From The University of Texas M.D. Anderson Cancer Center, Houston, TX; Medical Oncology Department, Vall d'Hebron University Hospital, Barcelona; Servicio Oncologia, Hospital Clinico Universitario, Valencia; Hospital Clinico San Carlos, Prof Martin Lagos S/N, Madrid, Spain; Memorial Sloan-Kettering Cancer Center, New York, NY; Department of Oncology and Hematology, University Hospital, Modena, Italy; Centre Georges-François Leclerc, Dijon, France; Weill Cornell Medical College/New York Presbyterian Hospital, New York, NY; Dana-Farber Cancer Institute, Boston, MA; The Sarah Cannon Cancer Center, Nashville, TN; Institut Paoli-Calmettes, Centre Regional de Lutte Contre le Cancer, Service d'Oncologie Medicale 2, Marseille, France; and Bristol-Myers Squibb, Princeton, NJ

Address reprint requests to Eva Thomas, MD, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030; e-mail: est5151{at}yahoo.com

Purpose Ixabepilone (BMS-247550) is an epothilone analog that optimizes the properties of naturally occurring epothilone B. Natural epothilones and their analogs promote tumor cell death by binding to tubulin and stabilizing microtubules, causing apoptosis. This international phase II trial assessed the activity of ixabepilone in patients with metastatic breast cancer (MBC) that was resistant to taxane therapy.

Patients and Methods MBC patients, who had experienced disease progression while receiving or within 4 months of taxane therapy (6 months if adjuvant taxane only), and who had a taxane as their last regimen, received ixabepilone (1- or 3-hour infusion of 50 mg/m² or 3-hour infusion of 40 mg/m² every 3 weeks).

Results Of 49 patients treated with 40 mg/m² ixabepilone during 3 hours, 35 (73%) had experienced disease progression within 1 month of their last taxane dose. The response rate was 12% (95% CI, 4.7% to 26.5%). All responses (n = 6) were partial; five of six patients had not responded to prior taxane therapy. In responders, the median response duration was 10.4 months. In 20 patients (41%), stable disease was the best outcome. Median time to progression was 2.2 months (95% CI, 1.4 to 3.2 months); median survival was 7.9 months. For treated patients across all cohorts (intent-to-treat population), the response rate was also 12% (eight of 66). Treatment-related adverse events in the study were manageable and primarily grade 1/2. Treatment-related neuropathy was mostly sensory and mild to moderate.

Conclusion Ixabepilone (40 mg/m² as a 3-hour infusion every 3 weeks) demonstrates promising antitumor activity and an acceptable safety profile in patients with taxane-resistant MBC.

published online ahead of print at www.jco.org on July 2, 2007.

Supported by Bristol-Myers Squibb (editorial).

Presented in part at the 39th Annual Meeting of the American Society of Clinical Oncology, May 31-June 3, 2003, Chicago, IL.

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

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