PREDICTION OF CARBOPLATIN CLEARANCE CALCULATED BY PATIENT CHARACTERISTICS OR 24-HOUR CREATININE CLEARANCE - A COMPARISON OF THE PERFORMANCEOF 3 FORMULAS

Purpose: Carboplatin doses can be individualized using the formula of Calvert et al. (Calvert formula) dose (mg) = area under the plasma con centration versus time curve (AUC).[glomerular filtration rate (GFR) 25]. Creatinine clearance (Ccr), either measured by the 24-h method o r calculated by the formula of Cockcroft and Gault [Cockcroft-Gault (C G) formula], is often substituted for the GFR. The CG formula is based on patient weight, age and sex, and the serum creatinine (Cr) concent ration. Another method for predicting carboplatin clearance (CL) using patient characteristics has also been proposed by Chatelut et al. (Ch atelut formula). This study was undertaken to evaluate the performance of the three formulae in predicting standard- and low-dose carboplati n pharmacokinetics. Methods: A total of 52 patients with advanced lung cancer were enrolled in this pharmacokinetic study; 37 received stand ard-dose carboplatin and 25 received low-dose carboplatin. The Cr conc entration was measured using an enzymatic assay. The three formulae we re used to predict carboplatin CL. The median absolute percent error ( MAPE) for each formula was evaluated by comparing the calculated and o bserved CL. For comparison of AUCs, free platinum plasma concentration s were measured at intervals up to 24 h after carboplatin administrati on. AUCs were determined and compared with predicted values. Results: In the standard-dose carboplatin group, the MAPEs for the prediction o f carboplatin CL from the 24-h Calvert, CG-Calvert and Chatelut formul ae were 13%, 12% and 23%, respectively. In the low-dose carboplatin gr oup, the corresponding MAPEs were 27%, 18% and 44%, respectively. Obse rved standard-dose carboplatin AUCs after aiming for target AUCs of 5 and 6 mg.min/ml using the Calvert formula based upon the 24-h Ccr were 5.3 +/- 0.8 and 5.9 +/- 0.8, respectively, indicating a small and acc eptable bias compared with that predicted from the dosing formula. Con clusions: The pharmacokinetics of standard-dose carboplatin were accur ately predicted by the Calvert formula based upon either 24-h or CG-ca lculated Ccr, but not by the Chatelut formula. Either CG-calculated or 24-h Ccr can be substituted for the GFR in the Calvert formula for th e determination of individual doses. The poor predictability of the Ch atelut formula found in this study might be the result of a difference s in either the Cr assay or the patient population. Therefore, formula e which attempt to estimate GFR are not necessarily valid if either th e Cr assay or the patient population is changed.