The European Paediatric Oncology off-patent medicines Consortium (EPOC) pharmacokinetic/pharmacodynamic study of doxorubicin

Boddy, AV; Steel, AJ; Boos, J; Krischke, M; Andre, N; Bisogno, G; Hempel, G; Bode, G; D'Incalci, M; Kontny, N

doi:10.1158/1538-7445.AM2013-2219

The European Paediatric Oncology off-patent medicines Consortium (EPOC) pharmacokinetic/pharmacodynamic study of doxorubicin

Lookup NU author(s): Professor Alan Boddy, Dr Alison Steel ORCiD

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Abstract

Background: Doxorubicin is a key component of a number of treatment regimens used in paediatric oncology despite the very limited pharmacology data on which current dosing regimens are based. In recognition of this, doxorubicin was included on the EMA priority list for paediatric off-patent medicines for which more information was required, particularly on pharmacokinetics.Methods: The EPOC consortium, with collaborators in the UK, France, Germany and Italy, performs paediatric oncology pharmacology clinical trials. This study is a multicentre, multinational phase II pharmacokinetic study investigating age-dependency in the clearance of doxorubicin in children with solid tumours and leukaemia. All patients are being treated according to a tumour-specific national or European therapeutic trial. The aim was to recruit 100 patients, with a particular focus on children less than 3 years. The plasma levels of markers such as troponin T, are being measured to evaluate their use as clinical markers for cardiotoxicity. Data is being analysed using a population pharmacokinetic approach and the impact of pharmacogenetics is being investigated.Results: The study has been open to recruitment in 20 clinical centres across the four participating countries. The target 100 patients have been recruited from all the contributing study protocols, with 26 patients less than 3 years. Of these 26 patients, 5 patients are less than 1 year. An interim pharmacokinetic analysis has been performed on the data from the first 31 patients. The results of the analysis are consistent with the primary aims of the overall study.Conclusion: The data generated during this study should provide comparative data on the age-dependent pharmacokinetics and pharmacogenetics of doxorubicin. The results will contribute to optimising the safe use of doxorubicin in children with cancer.Acknowledgements: Study funded under the seventh framework programme of the European Commission (FP7)