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Potential clinical applications of epothilones: a review of phase II studies

J M G Larkin1, S B Kaye

  • 1Department of Medicine, The Royal Marsden Hospital, Sutton, Surrey, UK.

Annals of Oncology : Official Journal of the European Society for Medical Oncology
|October 13, 2007
PubMed
Abstract

Insights

Epothilones show promise as cancer treatments, particularly in taxane-resistant cases. Further randomized studies are needed to confirm their efficacy and safety in combination therapies.

Area of Science:

  • Oncology
  • Pharmacology
  • Clinical Trials

Background:

  • Epothilones are cytotoxic macrolides with a mechanism of action similar to taxanes.
  • They exhibit antitumor activity in taxane-resistant cancers.
  • Six epothilones are currently in early-stage clinical trials for cancer treatment.

Purpose of the Study:

  • To review phase II clinical data for epothilones ixabepilone, patupilone, and KOS-862.
  • To assess the safety and efficacy of these epothilones in various cancer types.
  • To identify potential roles for epothilones in cancer treatment, especially in resistant settings.

Main Methods:

  • Systematic review of phase II clinical studies from 2000-2006.
  • Data sourced from PubMed and major oncology conference proceedings.
  • Inclusion criteria: safety and efficacy data for ≥10 patients per tumor type in a standard phase II design.

Main Results:

  • Epothilones demonstrated activity in phase II trials for lung, ovarian, breast, prostate, and renal carcinomas, and non-Hodgkin's lymphoma.
  • Limited activity was observed in other tumor types.
  • Preliminary data suggest safe combination of epothilones with cytotoxic agents like carboplatin.

Conclusions:

  • Epothilones may serve as an alternative to taxanes in resistant cancers, pending confirmation of activity and acceptable toxicity.
  • Randomized trials are necessary to evaluate epothilones as single agents and in combination regimens.

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