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Investigating the potential impact of dose banding for systemic anti-cancer therapy in the paediatric setting based on pharmacokinetic evidence

Lookup NU author(s): Professor Gareth Veal

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


Abstract

© 2017 The Authors. Background To make systemic anti-cancer therapy (SACT) preparation more practicable, dose-banding approaches are currently being introduced in many clinical centres. The present study aimed to determine the potential impact of using recently developed National Health Service in England (NHSE) dose-banding tables in a paediatric setting. Methods Using pharmacokinetic parameters obtained from 385 drug administrations in 352 children aged from 1 month to 18 years, treated with five drugs (dactinomycin, busulfan, carboplatin, cyclophosphamide and etoposide), individual exposures (area under the plasma drug concentration versus time curve; AUC) obtained using doses rounded according to the published NHSE tables were calculated and compared with those obtained by standard dose calculation methods. Results For all five drugs, the relative variation between the NHSE dose and the recommended dose (RecDose) (standard individually calculated dose) was between −6% and +5% as expected. In terms of AUC, there was no statistically significant difference in precision between exposures obtained by the RecDose and those obtained with dose banding (absolute value of relative difference 15–34%). Conclusion Based on pharmacokinetic data for these five drugs, the results generated support the implementation of NHSE dose-banding tables. Indeed, inter-patient variability in drug clearance and exposure far outweighs the impact of relatively small drug dose changes associated with dose banding.


Publication metadata

Author(s): White-Koning M, Osborne C, Paci A, Boddy AV, Chatelut E, Veal GJ

Publication type: Article

Publication status: Published

Journal: European Journal of Cancer

Year: 2018

Volume: 91

Pages: 56-67

Print publication date: 01/03/2018

Online publication date: 12/01/2018

Acceptance date: 27/11/2017

Date deposited: 22/01/2018

ISSN (print): 0959-8049

ISSN (electronic): 1879-0852

Publisher: Elsevier Ltd

URL: https://doi.org/10.1016/j.ejca.2017.11.029

DOI: 10.1016/j.ejca.2017.11.029

PubMed id: 29335155


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