PACLITAXEL - A NEW ANTINEOPLASTIC AGENT FOR REFRACTORY OVARIAN-CANCER

The chemistry, pharmacology, pharmacokinetics, clinical efficacy, adve rse effects, and dosage of paclitaxel are reviewed. Paclitaxel is a di terpenoid taxane derivative found in the bark and needles of the weste rn yew, Taxus brevifolia. Although it shares some structural similarit ies with other natural alkaloids, it contains a unique taxane ring. It is also unique in that its mechanism of action involves interruption of mitosis by promoting and stabilizing microtubule formation. Paclita xel doses greater than 60 mg/sq m i.v. consistently produce mean peak plasma concentrations of 2-13 muM. Liver metabolism and biliary excret ion are probably responsible for most of the drug's elimination. In cl inical trials, paclitaxel has shown substantial activity against advan ced, refractory ovarian cancer, metastatic breast cancer, and lung can cer, Paclitaxel may slow the course of melanoma and is being investiga ted in patients with advanced head and neck cancer and gastrointestina l cancer. Neutropenia is the major dose-limiting toxic effect of pacli taxel. Other adverse effects include hypersensitivity reactions, cardi ac toxicity, and neurotoxicity. The recommended dosage for the treatme nt of recurrent metastatic ovarian cancer is 135 mg/sq m i.v. given ov er 24 hours every three weeks. It is recommended that neutrophil-count and platelet-count recovery be allowed to occur before the next treat ment cycle is begun. Paclitaxel's activity against refractory ovarian cancer has not been matched since the inclusion of cisplatin in treatm ent regimens.