Background and importance In 2016, the World Health Organization estimated that 41 million children aged <5 years were overweight. Clinicians are increasingly likely to have obese children requiring chemotherapy under their care. Optimal drug dosing for this population is unclear. Anthracyclines are often used in paediatric cancers and given its cardiotoxicity, optimising the dose is mandatory.
Aim and objectives To clarify the most adequate anthracycline dose in obese children with the available safety, effectiveness, pharmacokinetic and pharmacodynamic data.
Material and methods A systematic review was carried out in PubMed, Scopus and Web of Science in March 2019 with ‘obese OR obesity’ in the title and the name of each drug (daunorubicin/doxorubicin/epirubicin/idarubicin) in the topic or equivalent. Articles with a reference to the paediatric population in the title were included. Those that did not provide relevant information for the purpose of our study, written in a language other than English/Spanish and which did not allow conclusions to be made were excluded. Articles that used a different obesity criterion were selected when providing data of interest. Article references were reviewed to identify additional studies.
Results Fourteen articles were found. Ten were excluded because no dosage information was given or because of duplications. Four articles were analysed: three for doxorubicin and one for daunorubicin. The efficacy of doxorubicin was measured in one article in which the patient achieved complete remission using adjusted doses. No changes in the ECG were found during treatment or at 2 months or 2 years after treatment ended. No other specific toxicity was observed. The pharmacokinetics of doxorubicin are controversial. One article found no difference in clearance using adjusted weight versus actual weight; the other showed lower clearance in obese paediatric patients than in normal weight paediatric patients (p<0.05).
For daunorubicin and doxorubicin, pharmacokinetic in vitro models suggested that the presence of adipocytes markedly reduced the clearance of chemotherapy agents used as induction therapy in ALL.
Conclusion and relevance It seems that adjusted doses of anthracyclines in obese paediatric patients can be effective and safety but due to limited data, this recommendation must be taken with caution.
References and/or acknowledgements No conflict of interest.
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