Epothilones: a novel class of microtubule-stabilizing drugs for the treatment of cancer.
Microtubule-targeted anticancer drugs are effective in treating various cancers but are limited in use due to development of resistance and unacceptable toxicities. The epothilones are a novel class of microtubule-stabilizing anticancer drugs and may have a role in treating taxane-resistant cancers. Revised and updated data from several clinical studies for ixabepilone were recently published and subsequently resulted in ixabepilone becoming the first epothilone approved as monotherapy or in combination for treatment of locally advanced or metastatic breast cancer. BMS-310705, patupilone, KOS-862, KOS-1584 and ZK-EPO are epothilones that have been developed. Although peripheral sensory neuropathy and neutropenia are the dose-limiting toxicities for ixabepilone, these dose-limiting toxicities are ixabepilone specific. This review will discuss the current preclinical, clinical pharmacokinetic and pharmacodynamic, efficacy and toxicity data of the epothilones.
Trivedi
Meghana
M
UCSD Moores Cancer Center, 3855 Health Sciences Dr., La Jolla, CA 92093-0845, USA. mvtrivedi@ucsd.edu
Budihardjo
Imawati
I
Loureiro
Kirsten
K
Reid
Tony R
TR
Ma
Joseph D
JD
D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology; D002986:Clinical Trials as Topic / Q000706:statistics & numerical data; D004285:Dogs; D004354:Drug Screening Assays, Antitumor; D034261:Epothilones / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008870:Microtubules / Q000187:drug effects* / Q000648:ultrastructure; D009362:Neoplasm Metastasis; D009503:Neutropenia / Q000139:chemically induced; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced; D051381:Rats; D013329:Structure-Activity Relationship; D050257:Tubulin Modulators / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D034261:Epothilones; D050257:Tubulin Modulators; C430592:ixabepilone