Ixabepilone

Ixabepilone, a semi-synthetic epothilone, was approved by the FDA in October 2007 with capecitabine for metastatic or locally advanced breast cancer resistant to an anthracycline and a taxane (a 752-patient randomised trial showed longer progression-free survival than capecitabine alone) and as monotherapy after anthracycline, taxane and capecitabine failure. The EMA refused a marketing authorisation in 2008 on the balance of benefit and toxicity. Peripheral neuropathy is dose-limiting; the combination is contraindicated with hepatic impairment because of excess toxic deaths, and the Cremophor-based diluent requires premedication for hypersensitivity.