Ixabepilone-associated peripheral neuropathy: Data from across the phase II and III clinical trials

Linda T. Vahdat, Eva S. Thomas, Henri H. Roché, Gabriel N. Hortobagyi, Joseph A. Sparano, Louise Yelle, Monica N. Fornier, Miguel Martín, Craig A. Bunnell, Pralay Mukhopadhyay, Ronald A. Peck, Edith A. Perez

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19 Scopus citations

Abstract

Purpose Dose-limiting neuropathy is a major adverse event associated with most of the microtubule-stabilizing agentbased chemotherapy regimens. Ixabepilone, a semisynthetic analogue of the natural epothilone B, has activity against a wide range of tumor types. Peripheral neuropathy (PN), associated with ixabepilone treatment, is usually mild to moderate, predominantly sensory and cumulative. Preclinical studies demonstrate that ixabepilone and taxanes produce a similar neurotoxicity profile. Methods We searched databases of phase II/III clinical trials involving patients receiving ixabepilone as a monotherapy or in combination with capecitabine for incidences of neuropathy. Potential risk factors for grade 3/4 PN were identified by a Cox regression analysis on a dataset of 1,540 patients with different tumor types across multiple studies. Results Rates for incidence of ixabepilone-induced severe PN (Common Terminology Criteria for Adverse Events grade 3/4) ranged from 1% in early untreated breast cancer up to 24% in heavily pretreated metastatic breast cancer; grade 4 PN was rare (≤1%). Common symptoms included numbness, paresthesias, and sometimes dysesthesias. Cox regression analysis identified only preexisting neuropathy as a risk factor for increased ixabepilone-associated PN. The management of PN has been primarily through dose adjustments (dose delays and/or dose reduction). Patients had resolution of their neuropathy within a median time of 5 to 6 weeks. Conclusions PN is a dose-limiting toxicity associated with ixabepilone treatment, is reversible in most patients, and can be managed with dose reduction and delays.

Original languageEnglish (US)
Pages (from-to)2661-2668
Number of pages8
JournalSupportive Care in Cancer
Volume20
Issue number11
DOIs
StatePublished - Nov 1 2012

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Keywords

  • Breast cancer
  • Epothilone
  • Ixabepilone
  • Microtubules
  • Neuropathy

ASJC Scopus subject areas

  • Oncology

Cite this

Vahdat, L. T., Thomas, E. S., Roché, H. H., Hortobagyi, G. N., Sparano, J. A., Yelle, L., Fornier, M. N., Martín, M., Bunnell, C. A., Mukhopadhyay, P., Peck, R. A., & Perez, E. A. (2012). Ixabepilone-associated peripheral neuropathy: Data from across the phase II and III clinical trials. Supportive Care in Cancer, 20(11), 2661-2668. https://doi.org/10.1007/s00520-012-1384-0