Evaluation of renal function and carboplatin clearance in Japanese cancer patients

Abstract

2556 Background: There is a close relationship between carboplatin clearance and glomerular filtration rate (GFR). Calvert developed the following formula for the dosing of carboplatin: dose (mg) = target area under the concentration versus time curve (AUC, mg ml-1 min) × [GFR (ml min-1) + 25]. However, this formula has not been evaluated in Japanese population. In this study, we prospectively evaluated renal function and carboplatin clearance in Japanese cancer patients. Methods: GFR was measured by inulin clearance before chemotherapy. The dose of carboplatin was determined by Calvert's formula using adjusted 24-h creatinine clearance (Ccr) by adding 0.2 (mg dl-1) to serum creatinine. A pharmacokinetic study was performed during the first cycle of the chemotherapy. Blood samples were obtained at 10 points within 24 hours. The observed AUC of carboplatin and the observed carboplatin clearance were calculated. Results: Inulin clearance was estimated in 28 cancer patients. Estimation of renal function with adjusted 24-h Ccr and estimated GFR equation (eGFR) were unbiased [mean prediction error (MPE) = -2.3%, 5.2% respectively] and acceptably precise [root mean squared error (RMSE) = 23.7%, 25.7% respectively], whereas non-adjusted Ccr and the Cockcroft-Gault equation overestimated GFR (MPE = 24.2%, 12.5% and RMSE = 37.2%, 32.7% respectively). Observed carboplatin clearance was proportional to GFR in range of renal function in this study (r = 0.903) and we verified the linearity. Non-renal clearance of carboplatin in Japanese cancer patients was 5.6 (ml min-1). Conclusions: 24-h Ccr adjusted by adding 0.2 (mg dl-1) to serum creatinine and eGFR were useful in assessing renal function for carboplatin dosing. It was suggested that non-renal clearance of carboplatin in Japanese cancer patients was less than 25 (ml min-1). No significant financial relationships to disclose.