Epothilones in prostate cancer.

Abstract

OBJECTIVES:

Treatment options for castration-resistant prostate cancer (CRPC) are limited. Although taxane-based regimens offer limited survival benefits, patients frequently relapse, and there are no standard regimens beyond progression. The epothilones represent a new class of chemotherapeutics that stabilize microtubules but have a distinct mechanism of action to the taxanes and low susceptibility to drug resistance. This article seeks to provide a review of what is currently known about the preclinical and clinical activity of this emerging class of agents.

MATERIALS AND METHODS:

A literature search was conducted using PubMed and congress abstract databases to identify clinical data relevant to the epothilones and their use in CRPC. Preference was given to recently published, well-designed preclinical reports and clinical studies.

RESULTS:

Preclinical activity has been shown for several epothilones in taxane-resistant cell lines across several tumors, including CRPC. Ixabepilone, sagopilone, and patupilone have demonstrated clinical activity and tolerability in phase II CRPC trials.

CONCLUSION:

The epothilones have demonstrated efficacy in CRPC, and ongoing studies will help define their roles in this disease state, including optimal dosing, combination regimens, and clinical biomarkers of response.

• Authors: William K Kelly
• Journal: Urologic oncology (Urol Oncol) 2011 Jul-Aug Vol. 29 Issue 4 Pg. 358-65 ISSN: 1873-2496 [Electronic] United States
• PMID: 19914096 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
• Copyright: Copyright © 2011 Elsevier Inc. All rights reserved.

Chemical References

• Antineoplastic Agents
• Benzothiazoles
• Epothilones
• ixabepilone
• sagopilone
• epothilone B

Topics

• Animals
• Antineoplastic Agents (therapeutic use)
• Benzothiazoles (therapeutic use)
• Drug Resistance, Neoplasm (drug effects)
• Epothilones (therapeutic use)
• Humans
• Male
• Prostatic Neoplasms (drug therapy, pathology)