Prospective Validation of Renal Function–Based Carboplatin Dosing in Children With Cancer: A United Kingdom Children’s Cancer Study Group Trial

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Abstract
PURPOSE: Carboplatin dosing in adults with cancer is based on renal function. The purpose of the current study was to validate a previously developed pediatric carboplatin-dosing formula. PATIENTS AND METHODS: Thirty-eight pediatric patients were randomized to receive a carboplatin dose calculated according to surface area or a renal function–based dosing formula. On the next course of therapy, the alternative dosing method was used for each patient. Carboplatin pharmacokinetics (based on free plasma platinum concentrations) were measured after both courses. RESULTS: The mean observed areas under the carboplatin concentration–versus-time curve (AUCs) after renal function– and surface area–based dosing were 98% and 95% of the target AUCs, respectively. The variation in the observed AUC was significantly less after renal function–based dosing (F test, P = .02), such that 74% of courses had an observed AUC within ± 20% of the target value, versus 49% for courses after dosing according to surface area. Only one of 22 courses at the center with the most experience with renal function–based dosing was associated with an AUC outside ± 20% of the target value, versus nine of 22 courses after surface area–based dosing in the same center. There was a relationship (r2 = .71) between carboplatin AUC and thrombocytopenia in 10 neuroblastoma patients treated with a combination of carboplatin, vincristine, etoposide, and cyclophosphamide. CONCLUSION: Renal function–based carboplatin dosing in children results in more consistent drug exposure than surface area–based drug administration.