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Generation of evidence-based carboplatin dosing guidelines for neonates and infants

Lookup NU author(s): Dr Shelby BarnettORCiD, Professor Deborah Tweddle, Professor Gareth Veal



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


© 2023, The Author(s). Background: To optimally dose childhood cancer patients it is essential that we apply evidence-based dosing approaches. Carboplatin is commonly dosed to achieve a cumulative target exposure (AUC) in children, with target AUC values of 5.2–7.8 mg/ml.min defined. To achieve these exposures patients are dosed at 6.6 mg/kg/day or 4.4 mg/kg for patients <5 kg. The current study uses real world clinical pharmacology data to optimise body weight-based doses to effectively target AUCs of 5.2–7.8 mg/ml.min in infants. Methods: Carboplatin exposures were determined across 165 treatment cycles in 82 patients ≤10 kg. AUC and clearance values were determined by Bayesian modelling from samples collected on day 1. These parameters were utilised to assess current dosing variability, determine doses required to achieve target AUC values and predict change in AUC using the modified dose. Results: No significant differences in clearance were identified between patients <5 kg and 5–10 kg. Consequently, for patients <5 kg, 4.4 mg/kg dosing was not sufficient to achieve a target AUC of 5.2 mg/ml.min, with <55% of patients within 25% of this target. Optimised daily doses for patients ≤10 kg were 6 mg/kg and 9 mg/kg for cumulative carboplatin target exposures of 5.2 and 7.8 mg/ml.min, respectively. Conclusions: Adoption of these evidence-based carboplatin doses in neonates and infants will reduce drug exposure variability and positively impact treatment.

Publication metadata

Author(s): Barnett S, Makin G, Tweddle DA, Osborne C, Veal GJ

Publication type: Article

Publication status: Published

Journal: British Journal of Cancer

Year: 2023

Volume: 129

Pages: 1773–1779

Print publication date: 23/11/2023

Online publication date: 10/10/2023

Acceptance date: 26/09/2023

Date deposited: 30/10/2023

ISSN (print): 0007-0920

ISSN (electronic): 1532-1827

Publisher: Springer Nature


DOI: 10.1038/s41416-023-02456-y

PubMed id: 37816842


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Funder referenceFunder name
Cancer Research UK
Experimental Cancer Medicine Centre Network
Little Princess Trust
National Institute for Health Research