Docetaxel trihydrate

Docetaxel principally exerts its cytotoxic activity by promoting and stabilising microtubule assembly while simultaneously preventing microtubule depolymerisation. This results in inhibition of normal cell division. In vitro and in vivo, docetaxel has antineoplastic activity against a wide range of cancer cells, demonstrates synergistic activity with several antineoplastic agents and often has greater cytotoxic activity against human breast cancer cell lines than paclitaxel. Docetaxel, binds to and stabilizes tubulin, which prevents physiological microtubule depolymerization/disassembly and results in cell-cycle arrest at the G2/M phase and cell death. This agent also is known to inhibit the anti-apoptotic gene Bcl2 and to encourage the expression of p27, a cell-cycle inhibitor, and further pro-angiogenic factors such as vascular endothelial growth factor (VEGF). Docetaxel is mainly metabolized in the liver by the cytochrome P450 CYP3A4 and CYP3A5 subfamilies of isoenzymes, and its clearance has been shown to be related to body surface area and hepatic enzyme and alpha1 acid glycoprotein plasma levels.

The tolerability of docetaxel in comparative clinical trials was generally acceptable. Severe neutropenia affects most docetaxel recipients, with febrile neutropenia occurring in approximately one-eighth of patients. Dose-cumulative severe fluid retention was reported in docetaxel recipients, despite premedication with prophylactic corticosteroids. Other adverse events include asthenia, stomatitis, infections, neurosensory, cutaneous or gastrointestinal events, nail changes, severe fever in the absence of infection, myalgia and hypersensitivity reactions.