Managing Ixabepilone Adverse Events With Dose Reduction

Ixabepilone is a synthetic analogue of epothilone B approved for the treatment of patients with metastatic or locally advanced breast cancer in combination with capecitabine for cancer resistant to an anthracycline and a taxane, and as monotherapy for cancer resistant or refractory to anthracyclines, taxanes, and capecitabine. The principal dose-limiting adverse events (AEs) of ixabepilone's standard dose (40 mg/m2 administered by 3-hour infusion once every 3 weeks) are peripheral neuropathy, neutropenia, and fatigue. An effective strategy to manage ixabepilone-related AEs is dose reduction by 20% (from 40 to 32 to 25 mg/m2); this does not appear to affect treatment efficacy and enables continuation of treatment after recovery (grade 1 or resolved). When appropriate, treatment can be restarted with a 20% dose reduction (to 32 mg/m2). For heavily pretreated patients, especially those with a low performance status, 32 mg/m2 is an appropriate initial dose; the dose of capecitabine should also be lowered by 20%. Weekly ixabepilone (15-20 mg/m2 on days 1, 8, and 15 every 28 days) may have an improved tolerability profile, but prospective studies with a large number of patients are required to determine whether it has therapeutic benefit comparable with the current approved regimen. More information is required on dosage and scheduling of ixabepilone in combination with other agents, including novel targeted therapies.