Measured versus estimated glomerular filtration rate in the Calvert equation: influence on carboplatin dosing

Purpose. Carboplatin is frequently dosed to achieve a desired area under th e plasma concentration-time curve (AUC) by using the Calvert or Chatelut eq uations to estimate carboplatin clearance. Accurate determination of glomer ular filtration rate (GFR) is necessary to correctly calculate carboplatin clearance using the Calvert equation. In clinical practice, the Cockcroft-G ault formula is frequently used to estimate GFR, but this practice has been reported to under- and overestimate carboplatin clearance. The purpose of this trial was to compare determinations of carboplatin clearance using the Chatelut equation and four separate GFR determinations, including Tc-99m-D TPA, the Cockcroft-Gault formula, a 24-h urine collection and a 2-h urine c ollection. Methods: Carboplatin clearance was estimated in 21 previously un treated extensive-stage small-cell lung cancer patients. GFR was determined using Tc-99m-DTPA, the Cockcroft-Gault formula, 24-h urine collection and 2-h urine collection. Serum and urine creatinine concentrations were measur ed using enzymatic assays. The carboplatin clearance was then calculated by individually adding 25 to the four GFR determinations based on the Calvert equation, which states that carboplatin clearance equals GFR + 25 (nonrena l clearance). The carboplatin clearance was also estimated using the Chatel ut equation. The five determinations of carboplatin clearance were compared using Friedman's test and post-hoc Wilcoxon signed rank tests. Precision a nd bias for each carboplatin clearance determination were calculated assumi ng that Tc-99m-DTPA provided the most accurate measure of GFR. Results. A s tatistically significant difference was found between the five methods of e stimating carboplatin clearance (P < 0.001). No difference was found betwee n carboplatin clearance calculated using Tc-99m-DTPA and the Chatelut equat ion, the Cockcroft-Gault formula or the 2-h urine collection. The Chatelut equation provided more precision and less bias than the 2-h urine collectio n (median precision 20% and 30%, median bias -1% and -18%, respectively). C onclusion. Compared to Tc-99m-DTPA, the Chatelut equation more accurately e stimates carboplatin clearance than the Cockcroft-Gault formula, the 2-h ur ine collection and the 24-h urine collection. The greater negative bias fou nd for the latter three estimates of carboplatin clearance could result in underdosing of carboplatin.