A CLINICAL AND PHARMACOKINETIC STUDY OF THE COMBINATION OF CARBOPLATIN AND PACLITAXEL FOR EPITHELIAL OVARIAN-CANCER

The aim of this phase I study was to determine the maximum tolerated d ose of a 3-h infusion of paclitaxel, combined with carboplatin at a fi xed AUC of 7 mg ml(-1) min every 4 weeks for up to six cycles and to e valuate any possible pharmacokinetic interaction Twelve chemonaive pat ients with ovarian cancer were treated with paclitaxel followed by a 3 0-min infusion of carboplatin. Paclitaxel dose was escalated from 150 mg m(-2) to 225 mg m(-2) in cohorts of three patients. Carboplatin dos e was based on renal function. Pharmacokinetic studies were performed in nine patients (at least two at each dose level). A total of 66 cour ses were evaluable for assessment. Grade 3 or 4 neutropenia was seen i n 70% of the courses, however hospitalization was not required. Grade 3 or 4 thrombocytopenia occurred in 24% of the courses. Alopecia, myal gia and peripheral neuropathy were common but rarely severe. The pharm acokinetics of paclitaxel was non-linear and did not appear to be infl uenced by cc-administration of carboplatin. The AUC of carboplatin was 7.0 +/- 1.4 mg ml(-1) min, indicating that there was no pharmacokinet ic interaction, The combination of carboplatin and paclitaxel may be a dministered as first-line treatment for advanced ovarian cancer. Altho ugh myelosuppression is the dose-limiting toxicity of the component dr ugs, the severity of thrombocytopenia was less than anticipated, The r esults of this study, with only a small number of patients, need to be confirmed in future investigations.