A universal formula based on cystatin C to perform individual dosing of carboplatin in normal weight, underweight, and obese patients

Abstract

2527 Background: It has recently been shown that it is possible to improve the prediction of carboplatin clearance by adding plasma cystatin C level (cysC), an endogenous marker of glomerular filtration rate, to the other patient characteristics routinely used for carboplatin individual dosing, namely serum creatinine (Scr), body weight (BW), age, and sex. This multi-center pharmacokinetic study was performed to evaluate prospectively the benefit of using cysC for carboplatin individual dosing. Methods: The 357 patients included in the study were receiving carboplatin as part of established protocols. A population pharmacokinetic analysis was performed using the NONMEM program. Seven covariates were studied: Scr, cysC, age, sex, BW, ideal body weight, and lean body mass. Results: The best covariate equation was: carboplatin clearance (mL/min) = 105. (Scr/75)-0.433. (cysC/1.00)-0.290 . (BW/65)+0.547 . (age/56)-0.351 . 0.855sex, with Scr in μmol/L, cysC in mg/L, BW in kg, age in years, and sex = 0 for male. Using an alternative weight descriptor (ideal body weight or lean body mass) did not improve the prediction. This final covariate model was validated by bootstrap analysis. The bias (mean percentage error) and imprecision (mean absolute percentage error) were +2% and 15% respectively on the total population, and were of a similar magnitude in each of the three subgroups of patients defined according to their body mass index. Conclusions: For the first time, a unique formula is proposed for carboplatin individual dosing to patients which is shown to be equally valid for underweight, normal weight, and obese patients. No significant financial relationships to disclose.