Ovarian cancer is the most lethal gynecologic
malignancy; consequently, there is a need for effective
therapies.
Epothilones are microtubule-
stabilizing agents that inhibit cell growth. Currently,
patupilone and its four synthetic derivatives
ixabepilone, BMS-310705,
sagopilone, 20-desmethyl-20-methylsulfanyl
epothilone B and
epothilone D, as well as its derivative
KOS-1584, are under clinical evaluation. This is the first systematic review conducted in accordance with the
PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines that synthesizes all available data emerging from trials and evaluates the efficacy and safety of
epothilones in epithelial ovarian, primary fallopian tube, and primary peritoneal
cancer. Despite the fact that
epothilones have proven active in
taxane-resistant settings in preclinical models, it is not yet clear from Phase II/III studies reviewed here that their clinical activity is superior to that of
taxanes. Nevertheless, responses to
epothilones have been observed in
platinum-refractory/resistant
ovarian cancer patients. Moreover, despite the shared mechanism of action of
epothilones, their clinical profile seems clearly different, with
diarrhea being the most common dose-limiting toxicity encountered with
patupilone, whereas
neutropenia and sensory neuropathy are the most common toxic effects observed with the other
epothilones. In any case, randomized trials comparing
epothilones with standard treatments seem warranted to define further the role of these agents, whereas
biomarker analysis might further optimize patient selection.