Epothilones in the treatment of cancer.
Epothilones are cytotoxic macrolides with a similar mechanism of action to paclitaxel but with the potential advantage of activity in taxane-resistant settings in preclinical models. The epothilones ixabepilone, patupilone, BMS-310705, KOS-862 and ZK-EPO are in early clinical trials for cancer treatment. Phase I studies have shown that dose-limiting toxicities of epothilones are generally neurotoxicity and neutropoenia although initial studies with patupilone indicated that diarrhoea was dose limiting. Neuropathy induced by ixabepilone may be schedule dependent. Over 20 Phase II studies of epothilones in cancer treatment have been reported, and significant activity in taxane-sensitive tumour types (such as breast, lung and prostate cancers) has been noted. Response rates in taxane-refractory metastatic breast cancer are relatively modest, but ixabepilone and patupilone have shown promising efficacy in hormone-refractory metastatic prostate cancer and in taxane-refractory ovarian cancer.
Larkin
James M G
JM
The Royal Marsden Hospital, Downs Road, Sutton, Surrey, SM2 5PT, UK.
Kaye
Stanley B
SB
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D002986:Clinical Trials as Topic; D004334:Drug Administration Schedule; D004353:Drug Evaluation, Preclinical; D019008:Drug Resistance, Neoplasm; D034261:Epothilones / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D050257:Tubulin Modulators / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D034261:Epothilones; D050257:Tubulin Modulators; C430592:ixabepilone; C093788:epothilone B