Epothilones in prostate cancer.
OBJECTIVE
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.


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.


CONCLUSIONS
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.
Kelly
William K
WK
Department of Medicine and Surgery, Yale School of Medicine, Yale Comprehensive Cancer Center, New Haven, CT 06520, USA. william.kelly@jefferson.edu
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D052160:Benzothiazoles / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D034261:Epothilones / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology
D000970:Antineoplastic Agents; D052160:Benzothiazoles; D034261:Epothilones; C430592:ixabepilone; C530494:sagopilone; C093788:epothilone B