Document Detail

The epothilones: new therapeutic agents for castration-resistant prostate cancer.
MedLine Citation:
PMID:  21964003     Owner:  NLM     Status:  MEDLINE    
The management of castration-resistant prostate cancer (CRPC) presents a clinical challenge because of limitations in efficacy and durability with currently available therapeutics. The epothilones represent a novel class of anticancer therapy that stabilizes microtubules, causing cell death and tumor regression in preclinical models. The structure of the tubulin-binding site for epothilones is distinct from that of the taxanes. Moreover, preclinical studies suggest nonoverlapping mechanisms of resistance between epothilones and taxanes. In early-phase studies in patients with CRPC, treatment with ixabepilone, a semisynthetic analog of epothilone B, induced objective responses and prostate-specific antigen declines in men previously progressing on docetaxel-based regimens. Clinical activity has been observed in nonrandomized trials for patients with CRPC using ixabepilone in the first- and second-line settings as a single agent and in combination with estramustine. Patupilone and sagopilone were also shown to have promising efficacy in phase II clinical trials of patients with CRPC. All three epothilones appear to be well tolerated, with modest rates of neutropenia and peripheral neuropathy. The lack of crossresistance between epothilones and taxanes may allow sequencing of these agents. Evaluating epothilones in phase III comparative trials would provide much-needed insight into their potential place in the management of patients with CRPC.
Tanya B Dorff; Mitchell E Gross
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Review     Date:  2011-09-30
Journal Detail:
Title:  The oncologist     Volume:  16     ISSN:  1549-490X     ISO Abbreviation:  Oncologist     Publication Date:  2011  
Date Detail:
Created Date:  2011-10-21     Completed Date:  2012-04-26     Revised Date:  2013-06-27    
Medline Journal Info:
Nlm Unique ID:  9607837     Medline TA:  Oncologist     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1349-58     Citation Subset:  IM    
Division of Cancer Medicine and Blood Diseases, University of Southern California, Los Angeles, California, USA.
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MeSH Terms
Epothilones / chemistry,  pharmacology,  therapeutic use*
Prostatic Neoplasms / drug therapy*,  pathology,  surgery
Reg. No./Substance:

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