Epothilones: a novel class of microtubule-stabilizing drugs for the treatment of cancer

Future Oncol. 2008 Aug;4(4):483-500. doi: 10.2217/14796694.4.4.483.

Abstract

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.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / pathology
  • Clinical Trials as Topic / statistics & numerical data
  • Dogs
  • Drug Screening Assays, Antitumor
  • Epothilones / administration & dosage
  • Epothilones / adverse effects
  • Epothilones / chemistry
  • Epothilones / pharmacology
  • Epothilones / therapeutic use*
  • Female
  • Humans
  • Male
  • Mice
  • Microtubules / drug effects*
  • Microtubules / ultrastructure
  • Neoplasm Metastasis
  • Neutropenia / chemically induced
  • Peripheral Nervous System Diseases / chemically induced
  • Rats
  • Structure-Activity Relationship
  • Tubulin Modulators / adverse effects
  • Tubulin Modulators / chemistry
  • Tubulin Modulators / pharmacology
  • Tubulin Modulators / therapeutic use*

Substances

  • Antineoplastic Agents
  • Epothilones
  • Tubulin Modulators
  • ixabepilone