Pharmacokinetic and pharmacodynamic analysis of combined chemotherapy with carboplatin and paclitaxel for patients with ovarian cancer

Abstract

Background. This study was conducted to assess the utility of pharmacokinetic and pharmacodynamic analyses of carboplatin (CBDCA) and paclitaxel (TAX) employed for chemotherapy in ovarian cancer patients.

Methods. The pharmacokinetics and pharmacodynamics of chemotherapy with CBDCA and TAX were analyzed in 13 patients with ovarian cancers. The pharmacodynamic model, based on myelosuppression, was assessed in terms of concentrations of free platinum (free-Pt) and TAX in blood samples. TAX (175 mg/m²) was administered intravenously (i.v.) over 3 h, and CBDCA (target area under the concentration curve [AUC], 5 mg/ml×min) over 1 h. Free-Pt and TAX concentrations in blood samples were measured at several time points after administration.

Results. The nadirs of both the leukocyte and neutro-phil counts correlated significantly with the TAX AUC (AUCtax) and serum albumin level, and the percentage decrease in platelet count (pd-Plt) correlated significantly with AUCtax, free-Pt AUC (AUCpt), and the serum albumin level. A pharmacodynamic model corresponding to the nadirs of leukocytes and neutrophils and to pd-Plt was thus generated.

Conclusion. This pharmacodynamic model may allow the ready prediction, from AUCtax, AUCpt, and the serum albumin value, of the degree of myelosuppression with combined CBDCA and TAX chemotherapy.