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

Authors' Affiliations: ¹ Department of Pharmacy and Pharmacology, The Netherlands Cancer Institute/Slotervaart Hospital; ² Department of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, the Netherlands and ³ Faculty of Pharmaceutical Sciences, Utrecht University, Utrecht, the Netherlands

Requests for reprints: Corine Ekhart, Department of Pharmacy and Pharmacology, The Netherlands Cancer Institute/Slotervaart Hospital, Louwesweg 6, 1066 EC, Amsterdam, the Netherlands. Phone: 31-205124657; Fax: 31-205124753; E-mail: apcek{at}slz.nl.

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.

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