ESPN 50th Annual Meeting

ESPN 2017


 
Carboplatin dosing in children using estimate glomerular filtration rate: equation matters
MIRJAM ESTHER VAN DE VELDE 1 HESTER BLUFPAND 1 GERTJAN KASPERS 1 FLOOR ABBINK 1 BRAM WILHELM 1 GODEFRIDUS J. PETERS 1 BIRGIT STOFFEL-WAGNER 2 AREND BĂ–KENKAMP 1

1- VU UNIVERSITY MEDICAL
2- UNIVERSITäTSKLINIKUM BONN
 
Introduction:

Renal function-based carboplatin dosing results in more consistent drug exposure than flat dosing. We aimed to validate the Newell dosing equation using estimated glomerular filtration rate (GFR) and study which renal function marker most accurately predicts carboplatin clearance in children.  

Material and methods:

 In 30 children with a wide spectrum of solid tumours, 78 carboplatin clearance values were obtained from individual fits using NONMEM. Observed carboplatin clearance was compared with predicted clearance calculated according to the Newell dosing equation using three different GFR estimates, one creatinine-based (eGFR-Schwartz), one cystatin C-based (eGFR-CKiD1) and one based on creatinine and cystatin C (eGFR-CKiD2). Bias and precision of the predictions was examined.

Results:

 Both CKiD equations were accurate with a bias of 1.7 (95% CI -1.7 to 5.1) and -3.3 (95% CI -7.0 to 0.35) ml/min for respectively eGFR-CKiD1 and CKiD2, whereas the bias of eGFR-Schwartz significantly differed from zero (-16.2; 95% CI -21.5 to -10.9 mL/minute). eGFR-CKiD1 gave the lowest bias and imprecision, the other two eGFR equations showed overprediction of carboplatin clearance as reflected by negative bias and higher mean prediction error values. The proportion of variance in observed clearance that can be explained by the predicted clearance was lowest for Schwartz (R2=0.58), the explained variance was 0.65 for both CKiD equations.

Conclusions:

 The two cystatin C-based CKiD equations outperform the widely used creatinine-based Schwartz equation in predicting carboplatin clearance. We recommend the use of estimated GFR based on cystatin C for carboplatin dosing in children unless a gold standard GFR measurement is available.