Pharmaceutical aspects of docetaxel.

Clinical trials, pharmacokinetics, and pharmaceutical aspects of docetaxel are reviewed. In Phase I trials, the maximum tolerated dose of docetaxel ranged from 80 to 115 mg/m2. The main dose-limiting toxicity was brief neutropenia. These results led to a recommended dosage schedule in Phase II trials of 100 mg/m2 given by i.v. infusion over one hour every three weeks. Docetaxel exhibits linear pharmacokinetics and has an elimination half-life of about 12 hours. Patients with hepatic dysfunction have higher drug concentrations and more severe adverse effects. The overall response rate in Phase II trials in women with anthracycline-resistant breast cancer was 47%. Docetaxel is indicated for use in the treatment of locally advanced or metastatic breast cancer that has progressed during anthracycline-based therapy or relapsed during anthracycline-based adjuvant therapy. Docetaxel is commercially available as 20- and 80-mg formulations, but both yield the same drug concentration (10 mg/mL) when mixed with diluent. The actual drug concentration in each vial and the volume of diluent differ from those indicated on the vial labels to allow a final concentration of 10 mg/mL in the premixed solution, despite drug loss during preparation. To avoid dosage errors when the premixed solution is added to the infusion solution, calculations should be based on the amount of docetaxel per milliliter of premixed solution rather than on the total volume of premixed solution. Docetaxel is fairly easy to prepare and administer and is suitable for use on an outpatient basis.