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.


METHODS
This review summarizes current preclinical and clinical data on the safety and efficacy of the epothilones ixabepilone (BMS-247550) and patupilone (EPO906) 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 II setting. Phase III trials are needed to confirm the activity of the epothilones in tandem with docetaxel, given the experience to date.
Dawson
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Division of Hematology/Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA. nad103@gunet.georgetown.edu
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D000077143:Docetaxel; D034261:Epothilones / Q000494:pharmacology* / Q000627:therapeutic use*; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D017430:Prostate-Specific Antigen / Q000187:drug effects; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D043823:Taxoids / Q000494:pharmacology / Q000627:therapeutic use; D050257:Tubulin Modulators / Q000494:pharmacology* / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D034261:Epothilones; D043823:Taxoids; D050257:Tubulin Modulators; D000077143:Docetaxel; D017430:Prostate-Specific Antigen; C430592:ixabepilone; C093788:epothilone B