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

作者：Vahdat Linda T^*; Thomas Eva S; Roche Henri H; Hortobagyi Gabriel N; Sparano Joseph A; Yelle Louise; Fornier Monica N; Martin Miguel; Bunnell Craig A; Mukhopadhyay Pralay; Peck Ronald A; Perez Edith A

来源：Supportive Care in Cancer, 2012, 20(11): 2661-2668.

DOI：10.1007/s00520-012-1384-0

• Neuropathy
• Ixabepilone
• Epothilone
• Breast cancer
• Microtubules

Dose-limiting neuropathy is a major adverse event associated with most of the microtubule-stabilizing agent-based 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. %26lt;br%26gt;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. %26lt;br%26gt;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 (a parts per thousand currency sign1%). 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. %26lt;br%26gt;PN is a dose-limiting toxicity associated with ixabepilone treatment, is reversible in most patients, and can be managed with dose reduction and delays.

• 出版日期2012-11