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A clinical and pharmacokinetic study of the combination of carboplatin and paclitaxel for epithelial ovarian cancer

Siddiqui, N; Boddy, AV; Thomas, HD; Bailey, NP; Robson, L; Lind, MJ; Calvert, AH; (1997) A clinical and pharmacokinetic study of the combination of carboplatin and paclitaxel for epithelial ovarian cancer. BRIT J CANCER , 75 (2) 287 - 294.

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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 cc-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.

Type: Article
Title: A clinical and pharmacokinetic study of the combination of carboplatin and paclitaxel for epithelial ovarian cancer
Keywords: paclitaxel, carboplatin, phase I, ovarian cancer, COLONY-STIMULATING FACTOR, CELL LUNG-CANCER, PHASE-I, RANDOMIZED TRIAL, RENAL-FUNCTION, TAXOL, CISPLATIN, CARCINOMA, TOXICITY, INFUSION
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Oncology
URI: http://discovery.ucl.ac.uk/id/eprint/351829
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