Ontology highlight
ABSTRACT: Purpose
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.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.
SUBMITTER: Vahdat LT
PROVIDER: S-EPMC3461204 | biostudies-literature | 2012 Nov
REPOSITORIES: biostudies-literature
Vahdat Linda T LT Thomas Eva S ES Roché Henri H HH Hortobagyi Gabriel N GN Sparano Joseph A JA Yelle Louise L Fornier Monica N MN Martín Miguel M Bunnell Craig A CA Mukhopadhyay Pralay P Peck Ronald A RA Perez Edith A EA
Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer 20120302 11
<h4>Purpose</h4>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 pro ...[more]