Epothilones and the next generation of phase III trials for prostate cancer

While the phase II trials of epothilones are currently ongoing, ixabepilone (BMS-247550) and patupilone (EPO906) have provided the most convincing phase II data for activity in HRPC, including no cross-resistance with taxanes. This class of compounds is the only new chemotherapeutic to have provided the most advanced data in phase II settings in HRPC. Therefore, the logical next step will be to pursue definitive phase III trials to confirm the activity of epothilones in tandem with docetaxel, given the experience to date. Such trials will lay the foundation for defining the role of epothilones in the first- and second-line settings in HRPC. The distinct toxicity profiles of each of these drugs will probably influence their future development and combination therapy with existing chemotherapy regimens. Also, for the first time, phase III trials in rationally designed combinations of targeted therapeutics (SWOG 0421 and CALGB 9040) are being undertaken in the USA for patients with HRPC, under the auspices of the major cooperative groups. However, we will not be able to rapidly develop and provide these agents for patients with cancer unless there is a concerted and serious effort by all involved in the care of these patients to enrol them into key clinical trials investigating exciting new classes of compounds. © 2005 BJU International.