Originally published as JCO Early Release 10.1200/JCO.2006.09.7097 on July 2 2007

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Phase II Clinical Trial of the Epothilone B Analog, Ixabepilone, in Patients With Non–Small-Cell Lung Cancer Whose Tumors Have Failed First-Line Platinum-Based Chemotherapy

Johan Vansteenkiste, Primo N. Lara, Jr, Thierry Le Chevalier, Jean-Luc Breton, Philip Bonomi, Alan B. Sandler, Mark A. Socinski, Catherine Delbaldo, Brent McHenry, David Lebwohl, Ronald Peck, Mark Edelman

From the Respiratory Oncology Unit (Pulmonology), University Hospital Gasthuisberg, Leuven, Belgium; University of California Davis Cancer Center, Division of Hematology/Oncology, Sacramento, CA; Institut Gustave Roussy, Departement de Medecine Interne, Villejuif; Centre Hospitalier Général Belfort; Service d'oncologie, Hôpital Henri-Mondor, Créteil, France; Rush Cancer Institute, Section of Oncology, Chicago, IL; Division of Hematology/Medical Oncology, Vanderbilt University Medical Center, Nashville, TN; Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC; Bristol-Myers Squibb, Lawrenceville, NJ; and the Greenebaum Cancer Center, University of Maryland, Baltimore, MD

Address reprint requests to Johan Vansteenkiste, MD, PhD, Respiratory Oncology Unit (Pulmonology), University Hospital Gasthuisberg, Herestraat 49, B-3000 Leuven, Belgium; e-mail: johan.vansteenkiste{at}uz.kuleuven.ac.be

Purpose Ixabepilone is the first in a new class of antineoplastic agents, the epothilones and their analogs. This international, randomized, phase II trial assessed two administration schedules of ixabepilone as second-line therapy in patients with non–small-cell lung cancer (NSCLC).

Patients and Methods Patients had experienced disease progression after one prior cisplatin- or carboplatin-based chemotherapy regimen. Ixabepilone was administered as a single 32 mg/m² 3-hour infusion (77 patients; arm A) or a 6 mg/m² 1-hour infusion daily for 5 consecutive days (69 patients; arm B) in a 3-week cycle.

Results The intent-to-treat objective response rate was 14.3% in arm A and 11.6% in arm B. Median duration of response was 8.7 months (95% CI, 5.3 to 9.5 months) in arm A and 9.6 months (95% CI, 6.1 to 19.7 months) in arm B. Median time to progression was 2.1 months (95% CI, 1.4 to 2.8 months) for arm A and 1.5 months (95% CI, 1.4 to 2.8 months) for arm B. Median survival was 8.3 months (95% CI, 5.8 to 11.5 months) for arm A, and 7.3 months (95% CI, 5.7 to 11.7 months) for arm B; the 1-year survival rate (both cohorts) was 38%. Responses occurred in patients with taxane-pretreated and platinum-refractory tumors. Both regimens had an acceptable toxicity profile. Myelosuppression was manageable, manifesting primarily as neutropenia and leukopenia. Neuropathy was primarily sensory, generally mild to moderate in severity, and mostly reversible (both regimens).

Conclusion Single-agent ixabepilone had clinically relevant activity and an acceptable safety profile in patients with advanced NSCLC whose tumors had failed one prior platinum-based chemotherapy regimen.

Supported by Bristol-Myers Squibb Co.

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.

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

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• Ixabepilone and the Narrow Path to Developing New Cytotoxic Drugs
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  JCO 2007 25: 3389-3391 [Full Text]

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