Abstract
The chemistry, pharmacology, pharmacokinetics, clinical efficacy, adverse effects, and dosage of paclitaxel are reviewed. Paclitaxel is a diterpenoid taxane derivative found in the bark and needles of the western yew, Taxus brevifolia. Although it shares some structural similarities 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. Paclitaxel doses greater than 60 mg/sq m i.v. consistently produce mean peak plasma concentrations of 2-13 microM. Liver metabolism and biliary excretion are probably responsible for most of the drug's elimination. In clinical trials, paclitaxel has shown substantial activity against advanced, refractory ovarian cancer, metastatic breast cancer, and lung cancer. Paclitaxel may slow the course of melanoma and is being investigated in patients with advanced head and neck cancer and gastrointestinal cancer. Neutropenia is the major dose-limiting toxic effect of paclitaxel. Other adverse effects include hypersensitivity reactions, cardiac toxicity, and neurotoxicity. The recommended dosage for the treatment of recurrent metastatic ovarian cancer is 135 mg/sq m i.v. given over 24 hours every three weeks. It is recommended that neutrophil-count and platelet-count recovery be allowed to occur before the next treatment cycle is begun. Paclitaxel's activity against refractory ovarian cancer has not been matched since the inclusion of cisplatin in treatment regimens.
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