Epothilone-induced peripheral neuropathy: a review of current knowledge.

Context: Epothilones, belonging to the family of microtubule stabilizing agents, have shown prolonged remissions and improved survival in various types of refractory, treatment-resistant cancer. Ixabepilone (BMS-247550) is the main representative of these compounds. Peripheral neuropathy is a significant toxicity of epothilones, eventually resulting in dose modification and changes in the treatment plan.

Objectives: This review critically looks at the pathogenesis, incidence, risk factors, characteristics, and management of epothilone-induced peripheral neuropathy (EIPN). We also highlight areas of future research to pursue.

Methods: References were identified by searches of PubMed from 2000 until December 2010 with related terms.

Results: The mechanism underlying EIPN remains rather unclear. Damage to the ganglion soma cells and peripheral axons through disruption of microtubules of the mitotic spindle and by interference with the axonal transport in the affected neurons may significantly contribute to the pathogenesis of EIPN. As a result, epothilones primarily produce an axonal, dose-dependent, sensory distal peripheral neuropathy, which is reversible in most cases on discontinuation of treatment. The incidence of EIPN is mainly related to risk factors, including cumulative dose and probably pre-existing neuropathy. To date, apart from the use of dose reduction and schedule change algorithm, there is no effective treatment with neuroprotective agents for EIPN.

Conclusion: EIPN remains a very challenging area in the field of toxic neuropathies. As such, there is a need for further preclinical and prospective clinical studies to elucidate the pathogenesis of EIPN and provide further robust evidence on its incidence, course, and reversibility.