Application of epothilones in breast cancer therapy

Abstract

The taxanes that target microtubules are among the most active drugs in breast cancer treatment; however, resistance to these agents remains a significant issue for many patients. The epothilones are a novel class of nontaxane, microtubule-targeting agents, currently being evaluated in varying stages of clinical trials. Ixabepilone is the first epothilone analogue to receive US Food and Drug Administration approval in the United States for the treatment of metastatic breast cancer and as such will be the primary focus of this review. Multiple phase II trials evaluating ixabepilone in different populations of patients with metastatic breast cancer as well as a phase III trial in combination with capecitabine have recently been published. Phase II trials clearly demonstrate the activity of single-agent ixabepilone in both taxane-untreated and taxane-treated metastatic breast cancer. Although the highest activity was seen in early lines of therapy, there was also clear evidence of activity in heavily pretreated patients. Ixabepilone has also been evaluated in combination with capecitabine in a randomized, phase III trial demonstrating a benefit for the combination compared with single-agent capecitabine for patients resistant to anthracyclines and taxanes. In general, ixabepilone administered as a single-agent and in combination with capecitabine has been reasonably well tolerated.