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

Carboplatin is frequently dosed to achieve a desired area under the plasma concentration-time curve (AUC) by using the Calvert or Chatelut equations to estimate carboplatin clearance. Accurate determination of glomerular filtration rate (GFR) is necessary to correctly calculate carboplatin clearance using the Calvert equation. In clinical practice, the Cockcroft-Gault 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 99mTc-DTPA, the Cockcroft-Gault formula, a 24-h urine collection and a 2-h urine collection.

Carboplatin clearance was estimated in 21 previously untreated extensive-stage small-cell lung cancer patients. GFR was determined using 99mTc-DTPA, the Cockcroft-Gault formula, 24-h urine collection and 2-h urine collection. Serum and urine creatinine concentrations were measured 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 (nonrenal clearance). The carboplatin clearance was also estimated using the Chatelut equation. The five determinations of carboplatin clearance were compared using Friedman's test and post-hoc Wilcoxon signed rank tests. Precision and bias for each carboplatin clearance determination were calculated assuming that 99mTc-DTPA provided the most accurate measure of GFR.

A statistically significant difference was found between the five methods of estimating carboplatin clearance (P < 0.001). No difference was found between carboplatin clearance calculated using 99mTc-DTPA and the Chatelut equation, the Cockcroft-Gault formula or the 2-h urine collection. The Chatelut equation provided more precision and less bias than the 2-h urine collection (median precision 20% and 30%, median bias -1% and -18%, respectively).

Compared to 99mTc-DTPA, the Chatelut equation more accurately estimates carboplatin clearance than the Cockcroft-Gault formula, the 2-h urine collection and the 24-h urine collection. The greater negative bias found for the latter three estimates of carboplatin clearance could result in underdosing of carboplatin.