Designing Chemotherapy Dosing Patterns in Pediatric Oncology: Current Strategies and Future Directions

Chemotherapy dosing in children usually begins with body size, but body size alone does not reliably predict drug exposure or toxicity across pediatric development. This review synthesizes current evidence to guide dosing approaches in pediatric oncology. Well-established approaches to optimizing cancer drug therapy include adjusting thiopurine doses based on TPMT and NUDT15 genetic profiles; using target drug exposure levels to guide Busulfan and carboplatin dosing; monitoring high-dose Methotrexate concentrations and administering leucovorin rescue; and measuring asparaginase activity levels in specific treatment protocols. In contrast to fixed-dose regimens, maintenance therapy for acute lymphoblastic leukemia uses a dynamic approach in which treatment intensity is titrated according to each patient's hematologic tolerance. Three dosing concepts, including dose modification, prospective dose individualization, and dose optimization during drug development, are frequently used interchangeably, but they represent distinct approaches that must be distinguished carefully. Machine-learning prediction tools, point-of-care pharmacokinetic systems, and closed-loop dosing remain in their early stages.