Epothilones in prostate cancer: review of clinical experience

Background: Hormone-refractory prostate cancer (HRPC) is a progressive chemotherapy-resistant disease that remains a challenge to manage, Despite the recent approval of docetaxel (Taxotere) for the treatment of HRPC, the need exists for additional novel agents that can further improve patient outcomes. The epothilones are potent antimicrotubule agents that have demonstrated activity in the setting of taxane resistance. They are structurally distinct compounds that appear to lack cross-resistance with the taxanes. Design: This review summarizes current preclinical and clinical data on the safety and efficacy of the epothilones ixabepilone (BMS-247550) and patupilone (EP0906) for the treatment of prostate 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 potent antitumor activity in vitro and in experimental animal models of prostate cancer. In clinical studies, the epothilones have demonstrated potent activity in HRPC, including no cross-resistance with the taxanes and a manageable toxicity profile. Phase II studies of single-agent ixabepilone in patients with HRPC have reported a confirmed prostate-specific antigen (PSA) response rate of 33%. Higher PSA response rates have been reported in studies that assessed the combination of ixabepilone and estramustine in patients with HRPC. Conclusions: The epothilones are promising new chemotherapeutic agents that have demonstrated single-agent antitumor activity in HRPC; in the phase 11 setting. Phase III trials are needed to confirm the activity of the epothilones in tandem with docetaxel, given the experience to date.