This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ekhart, C. Articles by Beijnen, J. H. Search for Related Content PubMed PubMed Citation Articles by Ekhart, C. Articles by Beijnen, J. H.

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.

This article has been cited by other articles:

				A. Schmitt, L. Gladieff, A. Lansiaux, C. Bobin-Dubigeon, M.-C. Etienne-Grimaldi, M. Boisdron-Celle, F. Serre-Debauvais, F. Pinguet, A. Floquet, E. Billaud, et al. A Universal Formula Based on Cystatin C to Perform Individual Dosing of Carboplatin in Normal Weight, Underweight, and Obese Patients Clin. Cancer Res., May 15, 2009; 15(10): 3633 - 3639. [Abstract] [Full Text] [PDF]

				S. S Shord, L. R Bressler, L. Radhakrishnan, N. Chen, and J L. Villano Evaluation of the Modified Diet in Renal Disease Equation for Calculation of Carboplatin Dose Ann. Pharmacother., February 1, 2009; 43(2): 235 - 241. [Abstract] [Full Text] [PDF]

				S. R. McWhinney, R. M. Goldberg, and H. L. McLeod Platinum neurotoxicity pharmacogenetics Mol. Cancer Ther., January 1, 2009; 8(1): 10 - 16. [Abstract] [Full Text] [PDF]

				R. H.J. Mathijssen, F. A. de Jong, W. J. Loos, J. M. van der Bol, J. Verweij, and A. Sparreboom Flat-Fixed Dosing Versus Body Surface Area Based Dosing of Anticancer Drugs in Adults: Does It Make a Difference? Oncologist, August 1, 2007; 12(8): 913 - 923. [Abstract] [Full Text] [PDF]