A Trial to Evaluate Epothilone D in Patients With Advanced Solid Tumors

Epothilone D represents one of a class of cytotoxic macrolides capable of causing mitotic arrest by stabilizing tubulin polymerization. Since microtubules are essential for mitosis, motility, secretion and proliferation, the observed antitumor effects of epothilones have been attributed to their ability to initiate cell death by inhibiting such processes. Epothilone D has demonstrated in vitro cytotoxic activity in a panel of human cell lines, equipotent to that of paclitaxel. In vivo, Epothilone D has also shown significant antitumor activity in a range of xenograft models, including paclitaxel-resistant xenografts. Epothilone D is more potent than paclitaxel in cell lines that demonstrate multiple drug resistant activity overexpressing p-glycoprotein.