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

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/m²) was administered intravenously (iv) over 1 h, and CPA (500 mg/m²) 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, a dose-limiting toxicity, for combined CBDCA and CPA chemotherapy. Received: June 19, 1997 / Accepted: July 27, 1998