Cisplatin and carboplatin pharmacokinetics in a pediatric patient with hepatoblastoma receiving peritoneal dialysis

• Published in: Cancer chemotherapy and pharmacology Vol. 86; no. 3; pp. 445 - 449
• Main Authors: Nijstad, A. Laura, van Eijkelenburg, Natasha K. A., Kraal, Kathelijne C. J. M., Meijs, Marieke J. M., de Kanter, Clara T. M. M., Lilien, Marc R., Huitema, Alwin D. R.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01-09-2020; Springer Nature B.V
• Subjects: Antineoplastic Combined Chemotherapy Protocols - pharmacokinetics; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Area Under Curve; Cancer Research; Carboplatin; Carboplatin - administration & dosage; Chemotherapy; Child, Preschool; Children; Cisplatin; Cisplatin - administration & dosage; Dialysate; Dialysis; Dosage; Drug dosages; Drugs; End-stage renal disease; Health services; Hepatoblastoma - drug therapy; Hepatoblastoma - pathology; Humans; Kidney diseases; Kidney Failure, Chronic - therapy; Liver Neoplasms - drug therapy; Liver Neoplasms - pathology; Male; Medical treatment; Medicine; Medicine & Public Health; Oncology; Pediatrics; Peritoneal Dialysis; Peritoneum; Pharmacokinetics; Pharmacology; Pharmacology/Toxicology; Platinum; Prognosis; Remission; Short Communication; Therapeutic drug monitoring; Tissue Distribution; Toxicity; Carboplatin; Pharmacokinetics; Cisplatin; Hepatoblastoma; Peritoneal dialysis
• ISSN: 0344-5704; 1432-0843
• DOI: 10.1007/s00280-020-04130-z

Purpose
Cisplatin and carboplatin are frequently used drugs in the treatment of pediatric hepatoblastoma. Dosing guidelines for these drugs in children requiring peritoneal dialysis are lacking. Here, we describe the case of a 3-year-old boy with pre-existing end-stage renal disease on peritoneal dialysis, requiring treatment with cisplatin and carboplatin for hepatoblastoma.
Methods
Pharmacokinetic data were generated to support clinical dosing decisions, with the aim of adequate exposure and minimal toxicity. In the first chemotherapy cycle, 25% of the standard cisplatin dose and 75% of the carboplatin dose, calculated using the pediatric Calvert formula, were administered. Free platinum concentrations were determined in plasma ultrafiltrate and dialysate samples drawn after administration of cis- and carboplatin.
Results
Cisplatin was well tolerated and the observed AUC of cisplatin were 15.3 and 14.3 mg/L h in cycles 1 and 3, respectively. The calculated AUC of carboplatin in cycle 1 (9.8 mg/mL min) exceeded target AUC of 6.5 mg/mL min and toxicity was observed; therefore, the dose was reduced in cycles 2 and 3. The observed AUC in cycles 2 and 3 was 5.4 and 5.7 mg/mL min respectively. Platinum concentrations in the dialysate showed that 3–4% of the total dose of cisplatin and 10–12% of the total dose of carboplatin were excreted via peritoneal dialysis. Chemotherapy enabled extended hemihepatectomy and complete remission was achieved.
Conclusion
This report shows that it is feasible to measure AUCs for both drugs and to individualize the dose of these drugs according to the PK results and clinical parameters. Our advice for future cases would be to calculate the starting dose of carboplatin using the (pediatric) Calvert formula, assuming a dialytic clearance of zero, and to adjust the dose if required, based on therapeutic drug monitoring.