Docetaxel: a review of its pharmacology and clinical activity

Docetaxel (Rhône-Poulenc Rorer Pharmaceuticals Inc.), a new and novel taxoid, is a potent antitumor agent that promotes microtubule polymerization and inhibits tubulin depolymerization, resulting in the inability of cells to replicate. Docetaxel exhibits a broad spectrum of antitumor activity in vitro and in vivo. Phase II trials indicate a high degree of activity against advanced breast cancer, including anthracycline-resistant disease, and significant activity in advanced non-small cell lung, ovarian, head and neck, and pancreatic carcinomas and potential activity against other tumors as well. The recommended dosing regimens is 100 mg/m2 administered intravenously over one hour, with cycles repeated every three weeks. The most frequent hematologic side effect is neutropenia. Most nonhematologic side effects are generally mild to moderate in severity. Dermatologic side effects occur frequently, and fluid retention occurs with cumulative dosing. Premedication regimens with corticosteroids prevent significant hypersensitivity reactions and appear to be of value in ameliorating skin reactions and fluid retention. Docetaxel is currently being intensively evaluated in a phase II/III clinical program both as a single agent and as part of combination chemotherapy regimens and should prove to be clinically useful for a number of tumors.