Epothilones in breast cancer: review of clinical experience

Background: Drugs that target microtubules, including paclitaxel (Taxol) and docetaxel (Taxotere), are among the most commonly prescribed anticancer therapies. However, the utility of taxane-based therapies is limited by difficulties with formulation, administration, and resistance induced by P-glycoprotein. The epothilones are a novel class of antimicrotubule agents that have demonstrated antitumor activity in the setting of resistance. Design: This review summarizes clinical studies of epothilones in patients with metastatic breast cancer. Data were identified by searches of PubMed and the Proceedings of the American Society of Clinical Oncology annual meetings from 2000 to 2006. Results: The epothilones have demonstrated promising antitumor activity and manageable toxicity in phase 11 studies of heavily pretreated patients with metastatic breast cancer, including patients with resistance to taxanes and other cytotoxic agents. Neuropathy associated with ixabepilone appears to be schedule dependent and comparable to that observed with paclitaxel. Ixabepilone appears to be active in combination with capecitabine. Conclusions: Ongoing and planned trials promise to elucidate the benefits of ixabepilone in combination with other agents including capecitabine, bevacizurnalb, and trastuzumab in patients with metastatic breast cancer as well as those receiving neo-adjuvant therapy.