Bayesian estimate of vinorelbine pharmacokinetic parameters in elderly patients with advanced metastatic cancer

The objective of the present study was to determine the pharmacokinetic pro file of vinorelbine in patients 65 years or older with metastatic cancer in progression. Twelve patients were enrolled in this study. Vinorelbine was administered by a 10-min continuous infusion at a dose of 20-30 mg/m(2) thr ough a central venous catheter, Chemotherapy was repeated weekly. A total o f 46 courses of vinorelbine was studied. Each patient underwent pharmacokin etic evaluation during the first cycle of treatment, Toxicity evaluation wa s carried out before each course of chemotherapy, Plasma vinorelbine determ inations were performed by high-performance Liquid chromatography with spec trofluorometric detection, A Bayesian estimation of individual pharmacokine tic parameters was carried out using the nonlinear mixed-effect modeling ap proach as implemented in the NONMEM computer program. An open three-compart ment pharmacokinetic model with a zero order input rate was used to describ e the kinetics of vinorelbine, Area under the plasma-concentration time cur ve (AUC) normalized to a 30 mg/m(2) administered dose averaged 0.89 mg/lite r x h (coefficient of variation = 23.7%), The total plasma clearance averag ed 0.93 liter/h/kg (0.61-1.83 liter/h/kg; coefficient of variation = 38,6%) , The elimination half-life was 38.1 +/- 5.8 h, A high correlation was foun d between patient age and total clearance (r = -0,8; P < 0,001), The main h ematological toxicity observed was anemia in 11 patients. Neutropenia occur red in 50% of patients. Significant correlations were found between AUC and the decrease in the hemoglobin Level (r = 0.60) and between AUC and the de crease in the neutrophil count (r = 0,66), Thrombocytopenia was observed in only one patient, In conclusion, the age-related decrease in clearance fou nd in this study supports the design of a Phase I study of vinorelbine in p atients older than 65 years or perhaps 70 years.