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.
1. Diagnosis of histologically documented, advanced stage, primary or metastatic adult
solid tumors that are refractory to standard therapy or for which no curative
standard therapy exists. This includes but is not limited to cancers of the breast,
ovary, head and neck, esophagus, lung, gastrointestinal tract, and sarcomas.
2. Evidence of radiographically measurable or evaluable disease.
1. Pre-existing peripheral neuropathy of CTC Grade > 2 due to any cause.
2. Documented hypersensitivity reaction (CTC Grade > 2) to prior paclitaxel or other
therapy containing Cremophor.