Ixabepilone: in Locally Advanced or Metastatic Breast Cancer

Ixabepilone, an analogue of the natural product epothilone B, stabilizes microtubules resulting in cell cycle arrest and apoptosis. It is indicated for the treatment of locally advanced or metastatic breast cancer in the US. Ixabepilone has shown antitumour activity in tumour cell lines in vitro and in several animal tumour models, including those that display key mechanisms of resistance to other anticancer agents. In a randomized, nonblind, multicentre, phase III trial in women with locally advanced or metastatic breast cancer that was pretreated with, or resistant to, anthracyclines and resistant to taxanes, progression-free survival was significantly longer in ixabepilone plus capecitabine recipients compared with recipients of capecitabine monotherapy (median 5.8 vs 4.2 months). The response rate to ixabepilone monotherapy was 11.5% in a noncomparative, multicentre, phase II trial in women with locally advanced or metastatic breast cancer resistant to anthracyclines, taxanes and capecitabine. The most common grade 3 or 4 treatment-related adverse events in both trials were myelosuppression and peripheral sensory neuropathy.