A formula for predicting optimal dosage of nedaplatin based on renal function in adult cancer patients

Heading

Abstract

Purpose. To predict the optimal dosage for nedaplatin (cis-diammineglycolatoplatinum), an anticancer drug and a platinum derivative like cisplatin and carboplatin, a simple formula was developed based on renal function in Japanese adult cancer patients.

Patients and methods. Unbound platinum concentrations in plasma after intravenous infusion of nedaplatin were measured for 187 courses in 145 patients with lung, esophageal, and cervical and ovarian cancer undergoing clinical treatment. The data were divided into two sets, a model development data set of 94 courses and a validation data set of 93 courses. Regression analysis was applied to the relationship between the unbound platinum clearance (CL) of nedaplatin and the patients' renal function. The predictability and usefulness of this formula were assessed by validation using the external data set of 93 courses obtained from 75 patients.

Results. A simple formula was obtained for predicting the platinum clearance using the creatinine clearance (CLcr): CL=0.0836×CLcr+3.45. Indices for the predictive performance for CL and the area under the plasma concentration curve (AUC) in the validation data were almost the same as those for the model development data.

Conclusions. A formula for predicting the CL of unbound platinum after nedaplatin administration was developed, and only CLcr was found to be a significant covariate of the CL. This formula was useful for estimating the CL for the second as well as the first treatment with nedaplatin.