Towards a model-based dose recommendation for doxorubicin in children

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2017

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Völler, S.
Hempel, G.
Würthwein, G.
Boddy, A.V.
Krischke, M.
Andre, N.
D'Incalci, M.
Bisogno, G.
Boos, J.

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Clinical Pharmacokinetics, 2017; 56(3):215-223

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Abstract

Following the publication of our paper regarding a population-based model of doxorubicin pharmacokinetics in children in Clinical Pharmacokinetics last year (Voller et al. 54:1139-1149, 2015), we have received many inquiries on the practical clinical consequences of this model; however, a population-based model is only one of the aspects to be taken into account when developing dosing algorithms. In addition, any new method of dose calculation would need clinical validation and, subsequently, a new clinical trial. However, such a trial, especially with regard to burden to the children involved, requires optimal preparation and the selection of the best hypotheses. The European Paediatric Oncology Off-Patent Medicines Consortium (EPOC), represented by the authors, would therefore like to initiate an interdisciplinary discussion on the clinical and pharmacological goals for dose calculation. This current opinion summarizes the existing knowledge on the pharmacokinetics and pharmacodynamics of doxorubicin. Our aim was to define the clinical needs as precisely as possible, with the intention of stimulating discussion between the clinical pediatric oncologist and the pediatric pharmacologist. By doing so, we hope to define surrogates for best practice of a common doxorubicin dose in children. The intent is for a trial to validate a rational dose calculation rule, leading to a regulatory process and subsequent labeling.

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Data source: Supplementary information, https://doi.org/10.1007/s40262-016-0451-y

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Copyright 2016 The Authors. This article is published with open access. This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/), which permits any noncommercial use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. (http://creativecommons.org/licenses/by-nc/4.0/)

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