Evaluation of a prediction model of cisplatin dose based on total platinum plasma concentration

The aim of this study was to validate prospectively a model of cisplatin dose adjustment. 27 patients (63 courses) with lung cancer were treated by a 5 day continuous infusion of cisplatin and etoposide. The dose of cisplatin was adjusted in order to reach a target plasma concentration of total platinum (TP) of 2000 mu/l at the end of the infusion. The target concentration was reached with a mean bias of 2.7% and a precision of 7.8%. The results were compared with those of a population of 38 patients (97 courses) with lung cancer and treated with the same protocol of chemotherapy, but without dose adjustment. The average dose adjustment was an increase of cisplatin dose of 20.2%. This augmentation was most important during the first course, decreasing during the following courses. There was also an increase in the etoposide AUC, although its dose was not modified. Toxicity to polymorphonuclear cells was significantly increased and was linked to etoposide AUC.