EPO906 (epothilone B): a promising novel microtubule stabilizer.

EPO906 (epothilone B) is a potent member of a new class of microtubule-stabilizing cytotoxic agents known as epothilones. Although structurally unrelated to the clinically validated taxanes, EPO906 acts similarly to promote the formation and stabilization of microtubules, arresting proliferating cells in mitosis, and eventually causing cell demise by apoptosis. In preclinical studies, EPO906 has shown anticancer activity both in vitro and in vivo against several cancer types, including models that are paclitaxel-resistant. Importantly, in contrast to the taxanes, EPO906 retained activity against cancer cells either overexpressing the P-glycoprotein efflux pump or bearing tubulin mutations. Two phase I studies with EPO906 were conducted to determine the safety and maximal tolerated dose on two different dosing schedules: weekly and every 3 weeks. Diarrhea was the dose-limiting toxicity on both schedules. Tumor responses were seen in colorectal cancer as well as a variety of other tumor types, such as breast, ovarian, lung, and carcinoid in these two phase I trials. Based on the promising results from phase I studies, phase II studies in numerous indications are ongoing. Copyright 2003 Elsevier Inc. All rights reserved.