Epothilones in the treatment of ovarian cancer

Abstract

Epothilones are a new group of microtubule-stabilizing agents that have demonstrated antitumor activity in taxane-resistant models. Taxanes remain some of the most active cytotoxic agents in current cancer therapy. Primary or acquired resistance to taxanes in tumor cells partly prevents their long-term efficacy. Certain side effects, such as myelosupression or irreversible neuropathy, can also limit prolonged taxane administration. Epothilone B (EPO906; patupilone), a natural compound, and its semisynthetic derivative, ixabepilone (BMS-247550), differ in their pharmacokinetic and toxicity profiles. Ovarian cancer patients frequently relapse after first-line treatment based on platinum–taxane doublets. Therefore, epothilones might represent a therapeutic alternative in this setting. Patupilone and ixabepilone have undergone parallel clinical development, but their future role in ovarian cancer therapeutics remains ill defined.