Originally published as JCO Early Release 10.1200/JCO.2008.17.7618 on April 6 2009

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Phase II Study of Eribulin Mesylate, a Halichondrin B Analog, in Patients With Metastatic Breast Cancer Previously Treated With an Anthracycline and a Taxane

From Weill Cornell Medical College, New York; State University of New York Upstate Medical University, Syracuse; and Stony Brook University Hospital, Stony Brook, NY; Harrington Cancer Center, Amarillo; El Paso Cancer Center, Texas Oncology PA and US Oncology, EI Paso; Baylor Charles A. Sammons Cancer Center, Texas Oncology PA and US Oncology, Dallas, TX; University of Kansas Medical Center, Kansas City, KS; Northwest Cancer Specialists, Vancouver, WA; Florida Cancer Research Institute, Davie, FL; Cancer Institute of New Jersey, New Brunswick; and Eisai Medical Research Inc, Ridgefield Park, NJ.

Corresponding author: Linda T. Vahdat, MD, Weill Medical College of Cornell University, Division of Hematology/Oncology, 425 E 61st St, 8th floor, New York, NY 10021; e-mail: ltv2001{at}med.cornell.edu.

Purpose Eribulin mesylate (E7389), a nontaxane microtubule dynamics inhibitor, is a structurally simplified, synthetic analog of the marine natural product halichondrin B. This open-label, single-arm, phase II study evaluated efficacy and tolerability of eribulin in heavily pretreated patients with metastatic breast cancer (MBC).

Methods MBC patients who were previously treated with an anthracycline and a taxane received eribulin mesylate (1.4 mg/m²) as a 2- to 5-minute intravenous (IV) infusion on days 1, 8, and 15 of a 28-day cycle. Because of neutropenia (at day 15), an alternative regimen of eribulin on days 1 and 8 of a 21-day cycle was administered. The primary end point was overall response rate.

Results Of the 103 patients treated, the median number of prior chemotherapy regimens was four (range, one to 11 regimens). In the per-protocol population (n = 87), eribulin achieved an independently reviewed objective response rate (all partial responses [PRs]) of 11.5% (95% CI, 5.7 to 20.1) and a clinical benefit rate (PR plus stable disease 6 months) of 17.2% (95% CI, 10.0 to 26.8). The median duration of response was 171 days (5.6 months; range, 44 to 363 days), the median progression-free survival was 79 days (2.6 months; range, 1 to 453 days), and the median overall survival was 275 days (9.0 months; range, 15 to 826 days). The most common drug-related grades 3 to 4 toxicities were as follows: neutropenia, 64%; leukopenia, 18%; fatigue, 5%; peripheral neuropathy, 5%; and febrile neutropenia, 4%.

Conclusion Eribulin demonstrated activity with manageable tolerability (including infrequent grade 3 and no grade 4 neuropathy) in heavily pretreated patients with MBC when dosed as a short IV infusion on days 1 and 8 of a 21-day cycle.

Supported in part by Eisai Medical Research Inc.

Presented in part at the 43rd Annual Meeting of the American Society of Clinical Oncology, June 1-5, 2007, Chicago, IL, and at the 2007 American Society of Clinical Oncology Breast Cancer Symposium, September 7-8, 2007, San Francisco, CA.

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

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