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

Br J Cancer. 1997;75(2):287-94. doi: 10.1038/bjc.1997.47.

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.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase I

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Carboplatin / administration & dosage*
  • Carboplatin / pharmacokinetics
  • Carcinoma / drug therapy*
  • Female
  • Hematopoiesis / drug effects
  • Humans
  • Middle Aged
  • Ovarian Neoplasms / drug therapy*
  • Paclitaxel / administration & dosage*
  • Paclitaxel / pharmacokinetics

Substances

  • Carboplatin
  • Paclitaxel