Pharmacokinetic and pharmacodynamic analysis of combined chemotherapy with carboplatin and cyclophosphamide in patients with gynecological cancers

Abstract

Background. This study was conducted to assess the utility of pharmacokinetic and pharmacodynamic analyses of chemotherapy with carboplatin (CBDCA) and cyclophosphamide (CPA). Methods. The pharmacokinetics (PK) and pharmacodynamics (PD) of chemotherapy with CBDCA and CPA were analyzed in 14 patients (12 with ovarian cancers and 2 with uterine cancers). The PD model based on myelosuppression was assessed in terms of concentrations of free platinum (free-Pt) and total CPA in blood samples. CBDCA (300 mg/m 2 ) was administered intravenously (iv) over 1 h, and CPA (500 mg/m 2 ) over 2 h. Free-Pt and CPA concentrations in blood samples were measured at several time points thereafter. Results. The nadirs of leukocyte and platelet counts were closely correlated with the free-Pt concentration 24 h after infusion (Pt-24), and with the CPA concentration 5 h after infusion (CPA-5). A PD model corresponding to the nadirs of leukocyte and platelet counts was thus generated.Conclusion. This PD model allowed ready prediction, from Pt-24 and CPA-5, of the degree of myelosuppression,

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

“…[13][14][15] In a previous study, we 16 found that pharmacokinetic and pharmacodynamic analysis of CBDCA/cyclophosphamide (CPA) chemotherapy for gynecological cancers allowed the prediction of n-Leu and n-Plt with only single measurements of free-Pt and CPA concentrations.…”

“…We also expect that this limited sampling model will prove useful for shortening the hospitalization period, thus helping to reduce costs. 16 Correlations between the AUCpt and hematological toxicity have been found in several pharmacodynamic studies of CBDCA. 11,12,17,18 Siddiqui et al 19 reported pharmacokinetic values for the combination of CBDCA and TAX for ovarian cancer.…”