PURPOSE: To determine the recommended dose of paclitaxel in chemotherapy used in combination with carboplatin, and to examine the pharmacokinetic parameters of paclitaxel and carboplatin in Japanese patients with epithelial ovarian cancer. METHODS: The study group comprised 18 patients (median age 53 years, range 30-67 years) who received a total of 28 courses of first-line chemotherapy. The paclitaxel levels were set at 150 mg/m(2) ( n=5), 175 mg/m(2) ( n=6) and 200 mg/m(2) ( n=7), with the fixed dose of carboplatin at AUC 5. The plasma concentrations of paclitaxel in 28 courses and platinum in 23 courses were measured to determine the in vivo pharmacokinetics parameters. RESULTS: The nadir of neutrophils in the paclitaxel 200 mg/m(2) group was significantly lower ( P<0.05) than in the 150 and 175 mg/m(2) groups. Of seven patients in the paclitaxel 200 mg/m(2) group, one had grade 3 myalgia, another grade 3 neuropathy, and two grade 4 neutropenia. Paclitaxel AUC and the peak level tended to be dose-dependent, clearly indicating a two-phase disappearance. Further, the paclitaxel dosage and paclitaxel AUC were also dose-dependent. Using a limited sampling protocol for carboplatin, the carboplatin AUC was found to change little in relation to the paclitaxel dosage. CONCLUSIONS: Based on the results of this clinical trial and pharmacokinetic study, 175 mg/m(2) of paclitaxel as a 3-h infusion in combination with carboplatin AUC 5 can be considered as the recommended dose for Japanese ovarian cancer patients.
RCT Entities:
PURPOSE: To determine the recommended dose of paclitaxel in chemotherapy used in combination with carboplatin, and to examine the pharmacokinetic parameters of paclitaxel and carboplatin in Japanese patients with epithelial ovarian cancer. METHODS: The study group comprised 18 patients (median age 53 years, range 30-67 years) who received a total of 28 courses of first-line chemotherapy. The paclitaxel levels were set at 150 mg/m(2) ( n=5), 175 mg/m(2) ( n=6) and 200 mg/m(2) ( n=7), with the fixed dose of carboplatin at AUC 5. The plasma concentrations of paclitaxel in 28 courses and platinum in 23 courses were measured to determine the in vivo pharmacokinetics parameters. RESULTS: The nadir of neutrophils in the paclitaxel 200 mg/m(2) group was significantly lower ( P<0.05) than in the 150 and 175 mg/m(2) groups. Of seven patients in the paclitaxel 200 mg/m(2) group, one had grade 3 myalgia, another grade 3 neuropathy, and two grade 4 neutropenia. Paclitaxel AUC and the peak level tended to be dose-dependent, clearly indicating a two-phase disappearance. Further, the paclitaxel dosage and paclitaxel AUC were also dose-dependent. Using a limited sampling protocol for carboplatin, the carboplatin AUC was found to change little in relation to the paclitaxel dosage. CONCLUSIONS: Based on the results of this clinical trial and pharmacokinetic study, 175 mg/m(2) of paclitaxel as a 3-h infusion in combination with carboplatin AUC 5 can be considered as the recommended dose for Japanese ovarian cancerpatients.
Authors: R C Doebele; P Conkling; A M Traynor; G A Otterson; Y Zhao; S Wind; P Stopfer; R Kaiser; D R Camidge Journal: Ann Oncol Date: 2012-02-16 Impact factor: 32.976
Authors: Weidong Lu; Ursula A Matulonis; Anne Doherty-Gilman; Hang Lee; Elizabeth Dean-Clower; Andrew Rosulek; Carolyn Gibson; Annekathryn Goodman; Roger B Davis; Julie E Buring; Peter M Wayne; David S Rosenthal; Richard T Penson Journal: J Altern Complement Med Date: 2009-07 Impact factor: 2.579