Calculating carboplatin doses using the 4-variable modification of diet in renal disease (4-v MDRD) estimate of glomerular filtration rate (GFR) in the Calvert formula

Abstract

2521 Background: The dose of carboplatin is usually calculated using the Calvert formula, with various bedside estimates utilized rather than directly measured GFR. The 4-v MDRD equation (Levey AS, et al. Ann Intern Med 2006; 145: 247–254) is now advocated as the routine method of estimating renal function from serum creatinine in all patients. Adoption in clinical practice is occurring despite lack of validation in oncology patients. The aim of this study was to compare carboplatin doses derived from the Calvert formula using measured GFR and the estimates of the 4-v MDRD equation and other established estimates. Methods: GFR was determined using technetium-99m diethyl triamine penta-acetic acid (Tc99mDTPA) clearance. Serum creatinine (Jaffe method) was measured and GFR estimates calculated using 4-v MDRD, Cockcroft and Gault formula (CGF), Wright, Martin, and Jelliffe (JF) formulae. Carboplatin doses were calculated using the Calvert formula, targeting an area under the curve of 7mg.ml- 1.min-1. Results: GFR was measured in 510 adult oncology patients (323 male, 187 female, mean age 63 years, range 17–87 years, mean GFR 84 mL/min, range 16–205 mL/min). The mean (range) carboplatin dose was 765 mg (287–1,610 mg), 681 mg (237–1,306 mg), 674 mg (249–2,044 mg), 721 mg (261–1,536mg), 741 mg (261–2,128mg), 620 mg (244- 1,329 mg) for measured GFR, 4-v MDRD, CGF, Wright, Martin, and JF formulas respectively. The accuracy (% within 20% of ‘true’ dose) was 58%, 63%, 73%, 72% and 49% for 4-v MDRD, CGF, Wright, Martin, and JF formulas respectively. Carboplatin doses derived using the 4-v MDRD estimate of GFR become increasingly less accurate with increasing GFR (see table ). All other formulas performed similarly. Conclusions: The 4-v MDRD equation resulted in an imprecise estimation of carboplatin doses with the degree of variability dependant on the level of renal function. [Table: see text] No significant financial relationships to disclose.