title: A clinical and pharmacokinetic study of the combination of carboplatin and paclitaxel for epithelial ovarian cancer.
abstract: The aim of this phase I study was to determine the maximum tolerated dose of a 3-h infusion of paclitaxel, combined with carboplatin at a fixed AUC of 7 mg ml-1 min every 4 weeks for up to six cycles and to evaluate any possible pharmacokinetic interaction. Twelve chemonaive patients with ovarian cancer were treated with paclitaxel followed by a 30-min infusion of carboplatin. Paclitaxel dose was escalated from 150 mg m-2 to 225 mg m-2 in cohorts of three patients. Carboplatin dose was based on renal function. Pharmacokinetic studies were performed in nine patients (at least two at each dose level). A total of 66 courses were evaluable for assessment. Grade 3 or 4 neutropenia was seen in 70% of the courses, however hospitalization was not required. Grade 3 or 4 thrombocytopenia occurred in 24% of the courses. Alopecia, myalgia and peripheral neuropathy were common but rarely severe. The pharmacokinetics of paclitaxel was non-linear and did not appear to be influenced by co-administration of carboplatin. The AUC of carboplatin was 7.0 +/- 1.4 mg ml-1 min, indicating that there was no pharmacokinetic interaction. The combination of carboplatin and paclitaxel may be administered as first-line treatment for advanced ovarian cancer. Although myelosuppression is the dose-limiting toxicity of the component drugs, the severity of thrombocytopenia was less than anticipated. The results of this study, with only a small number of patients, need to be confirmed in future investigations.
authors.affiliation: Nothern Centre for Cancer Treatment, Newcastle General Hospital, Newcastle upon Tyne, UK.
authors.forename: N
authors.initials: N
authors.lastname: Siddiqui
authors.forename: A V
authors.initials: AV
authors.lastname: Boddy
authors.forename: H D
authors.initials: HD
authors.lastname: Thomas
authors.forename: N P
authors.initials: NP
authors.lastname: Bailey
authors.forename: L
authors.initials: L
authors.lastname: Robson
authors.forename: M J
authors.initials: MJ
authors.lastname: Lind
authors.forename: A H
authors.initials: AH
authors.lastname: Calvert
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects; D016190:Carboplatin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002277:Carcinoma / Q000188:drug therapy*; D005260:Female; D006410:Hematopoiesis / Q000187:drug effects; D006801:Humans; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D017239:Paclitaxel / Q000008:administration & dosage* / Q000493:pharmacokinetics
chemical_list: D016190:Carboplatin; D017239:Paclitaxel