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Changes in Neurologic Function Tests May Predict Neurotoxicity Caused by Ixabepilone

James J. Lee, Jennifer A. Low, Earllaine Croarkin, Rebecca Parks, Arlene W. Berman, Nitin Mannan, Seth M. Steinberg, Sandra M. Swain

From the Cancer Therapeutics Branch, Medical Oncology Clinical Research Unit, and Biostatistics and Data Management Section, Center for Cancer Research, Cancer Therapy Evaluation Program; Division of Cancer Treatment and Diagnosis, National Cancer Institute; and Rehabilitation Medicine Department, National Institutes of Health, Bethesda, MD

Address reprint requests to Sandra M. Swain, MD, Cancer Therapeutics Branch, Center for Cancer Research, National Cancer Institute, Bldg 8, Rm 5101, 8901 Wisconsin Ave, Bethesda, MD 20889-5015; e-mail: swains{at}mail.nih.gov

PURPOSE: To investigate baseline factors and neurologic function tests (NFTs) that may predict the development of grade 2 or higher peripheral neuropathy (PN) after treatment with ixabepilone, an epothilone microtubule-stabilizing agent with antitumor activity.

PATIENTS AND METHODS: Advanced breast cancer patients were treated with ixabepilone (6 mg/m²) for 5 consecutive days every 3 weeks in a phase II clinical trial. Physical examinations, questionnaires, nerve conduction studies, and NFTs, including the Jebsen Test of Hand Function (JTH) and the Grooved Pegboard Test (GPT), were performed at baseline and during subsequent cycles.

RESULTS: Forty-seven patients assessable for PN received a median of five cycles of therapy (range, one to 22 cycles). Nine of these patients developed grade 2 PN, and two developed grade 3 PN, with a median time to onset of 144 days (range, 6 to 189 days). Among these 11 patients, PN resolved in eight patients, with a median of 15 days (range, 6 to 346 days) after onset, but PN did not resolve in three patients during follow-ups at 76, 361, and 746 days after onset. GPT and changes of JTH scores at onset of PN were significantly different between patients with and without PN at comparable follow-up times (P = .006 and P = .002, respectively). Changes in GPT and JTH scores over the first two cycles were often associated with the development of PN by exploratory actuarial analysis.

CONCLUSION: Serious ixabepilone-induced neuropathy was relatively rare on the treatment schedule used. NFTs, such as JTH and GPT, may have utility for predicting PN, but further testing is needed.

Supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research, Bethesda, MD.

J.J.L. and J.A.L. contributed equally to this work.

Presented in part at the 26th Annual San Antonio Breast Cancer Symposium, San Antonio, TX, December 3-6, 2003; and the 41st Annual Meeting of the American Society of Clinical Oncology, Orlando, FL, May 13-17, 2005.

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

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