PHARMACEUTICAL ASPECTS OF DOCETAXEL

Clinical trials, pharmacokinetics, and pharmaceutical aspects of docet axel are reviewed. In Phase I trials, the maximum tolerated dose of do cetaxel ranged from 80 to 115 mg/m(2). The main dose-limiting toxicity was brief neutropenia. These results led to a recommended dosage sche dule in Phase II trials of 100 mg/m(2) given by i.v. infusion over one hour every three weeks. Docetaxel exhibits linear pharmacokinetics an d has an elimination half-life of about 12 hours. Patients with hepati c dysfunction have higher drug concentrations and more severe adverse effects. The overall response rate in Phase II trials in women with an thracycline-resistant breast cancer was 47%. Docetaxel is indicated fo r use in the treatment of locally advanced or metastatic breast cancer that has progressed during anthracycline-based therapy or relapsed du ring anthracycline-based adjuvant therapy. Docetaxel is commercially a vailable as 20- and 80-mg formulations, but both yield the same drug c oncentration (10 mg/mL) when mixed with diluent. The actual drug conce ntration in each vial and the volume of diluent differ from those indi cated 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 sol ution, calculations should be based on the amount of docetaxel per mil liliter of premixed solution rather than on the total volume of premix ed solution. Docetaxel is fairly easy to prepare and administer and is suitable for use on an outpatient basis.