Cisplatin pharmacokinetics in a child receiving peritoneal dialysis

Cisplatin is a highly effective and frequently used drug in the chemotherapy of solid tumors in children, but there is currently no information to guide dosing in children requiring dialysis. Here, we present the case of a 2-year-old boy with end-stage renal disease managed with peritoneal dialysis and requiring cisplatin for a newly diagnosed hepatoblastoma. A pharmacokinetic study was performed to personalize the cisplatin dose with the goal of providing adequate cisplatin exposure and avoiding excessive exposure and toxicity. Accordingly, 25% of the standard cisplatin dose was infused intravenously over 4 h. Serial blood and peritoneal fluid samples were obtained, and free cisplatin levels were subjected to noncompartmental pharmacokinetic analysis. The disposition of free cisplatin was significantly altered as compared to that of normal children. Despite a 75% dose reduction, our patient showed a fourfold increase in free cisplatin exposure (AUC = 64.1 h mcg/mL) compared with the AUC observed in children with normal kidney (15 + or - 9 h mcg/mL) function. When a subsequent dose was decreased to 8.7% of the standard dose, the free cisplatin AUC measured 29.7 h mcg/mL and more closely approximated the exposure observed in children with normal kidney function.