Flat Dosing of Carboplatin Is Justified in Adult Patients with Normal Renal Function

Abstract

Purpose: The Calvert formula is a widely applied algorithm for the a priori dosing of carboplatin based on patients glomerular filtration rate (GFR) as accurately measured using the ⁵¹Cr-EDTA clearance. Substitution of the GFR in this formula by an estimate of creatinine clearance or GFR as calculated by formulae using serum creatinine (S_CR; Cockcroft-Gault, Jelliffe, and Wright) is, however, routine clinical practice in many hospitals. The goal of this study was to validate this practice retrospectively in a large heterogeneous adult patient population. Experimental Design: Concentration-time data of ultrafilterable platinum of 178 patients (280 courses, 3,119 samples) with different types of cancer receiving carboplatin-based chemotherapy in conventional and high doses were available. Data were described with a linear two-compartment population pharmacokinetic model. Relations between S_CR-based formulae for estimating renal function and carboplatin clearance were investigated. Results: None of the tested S_CR-based estimates of renal function were relevantly related to the pharmacokinetic variables of carboplatin. Neither S_CR (median, 51; range, 18-124 μmol/L) nor the estimated GFR using the three different formulae was related to carboplatin clearance. Conclusions: Our data do not support the application of modifications of the Calvert formula by estimating GFR from S_CR in the a priori dosing of carboplatin in patients with relatively normal renal function (creatinine clearance, >50 mL/min). For targeted carboplatin exposures, the original Calvert formula, measuring GFR using the ⁵¹Cr-EDTA clearance, remains the method of choice. Alternatively, in patients with normal renal function, a flat dose based on the mean population carboplatin clearance should be administered.