The epothilones are a novel class of anticancer agents that are active against taxane-sensitive and taxane-resistant breast cancer. Each of the epothilone analogues in development has demonstrated activity in women with anthracycline- and taxane-resistant metastatic breast cancer. Ixabepilone, the epothilone analogue that is furthest along in clinical development, shows promise both as monotherapy and in combination with other agents. The most common adverse events associated with ixabepilone are sensory neuropathy and neutropenia. Randomized phase III clinical trials are currently being conducted to evaluate its efficacy in combination with capecitabine for patients with advanced breast cancer. Patupilone and KOS-862, two other epothilone analogues, are currently in phase I and phase II clinical development. Despite their structural similarity to ixabepilone, these agents appear to have different toxicity profiles, with patupilone causing diarrhea rather than neurotoxicity or myelosuppression, and KOS-862 causing central nervous system and peripheral neurotoxicity. Though the therapeutic role of the epothilones has not yet been clearly defined, this new class of microtubule-targeting agents represent an important advance in the treatment of patients with breast cancer.

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