Dosing chemotherapy in children with obesity: literature review and evaluation of local practices.
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PURPOSE: Pediatric obesity is a growing public health concern, affecting drug pharmacokinetics, including chemotherapies. These challenges are amplified by the underrepresentation of children with obesity in clinical trials and the absence of clear dosing guidelines. METHODS: A retrospective, single-center cohort study was conducted at the Institute of Pediatric Hematology and Oncology (Lyon, France), including children with obesity (Body mass index > IOTF-30) treated with at least one intravenous chemotherapy between 2008 and 2022. Medical records were reviewed for patient characteristics, chemotherapy type, administered dose and adjustments. A literature review was performed using PubMed to evaluate chemotherapy dosing recommendations for children with obesity. RESULTS: A total of 248 chemotherapy courses for 113 children were analyzed, including 239 cytotoxic agents and 9 monoclonal antibodies. Most treatments were for hematological malignancies (n = 151), followed by solid tumors (n = 97). Only 45 chemotherapies (18%) were dose-adjusted in 19 patients (17%). Among these, 87% were capped at a body surface area (BSA) of 2 m², while 13% involved percentage-based reductions. Five adjustments were based on ideal body weight (IBW). Among the 25 patients with BSA > 2 m², 68% received adjusted doses, primarily through capping. In contrast, for patients with BSA < 2 m², dose reductions were rare and applied to avoid potential toxicity. The literature review revealed that total body weight (TBW) is generally used for dosing most chemotherapeutic agents, though certain drugs may require ideal body weight or adjusted body weight. CONCLUSION: Heterogeneity in clinical practice reflects the absence of standardized pediatric guidelines. Therapeutic drug monitoring and further pharmacokinetic studies may further help optimize dosing. TBW is recommended based on the study results and literature review, with exceptions, and guidelines should be widely disseminated to improve clinical practice.