title: Towards a Model-Based Dose Recommendation for Doxorubicin in Children.
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.
authors.affiliation: Department of Pharmaceutical and Medical Chemistry-Clinical Pharmacy, University of Münster, Corrensstraße 48, 48149, Münster, Germany.
authors.forename: Swantje
authors.initials: S
authors.lastname: Völler
authors.affiliation: Department of Pharmaceutical and Medical Chemistry-Clinical Pharmacy, University of Münster, Corrensstraße 48, 48149, Münster, Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: Hempel
authors.affiliation: Centre for Clinical Trials, ZKS Münster (BMBF 01KN1105), University Hospital Muenster, Von-Esmarch-Straße 62, 48149, Münster, Germany.
authors.forename: Gudrun
authors.initials: G
authors.lastname: Würthwein
authors.affiliation: Northern Institute for Cancer Research, Paul O'Gorman Building, Medical School, Newcastle University, Framlington Place, Newcastle upon Tyne, NE2 4HH, UK.|Faculty of Pharmacy, The University of Sydney, Sydney, NSW, 2006, Australia.
authors.forename: Alan V
authors.initials: AV
authors.lastname: Boddy
authors.affiliation: Centre for Clinical Trials, ZKS Münster (BMBF 01KN1105), University Hospital Muenster, Von-Esmarch-Straße 62, 48149, Münster, Germany.
authors.forename: Miriam
authors.initials: M
authors.lastname: Krischke
authors.affiliation: INSERM UMR 911, Centre de Recherche en Oncologie biologique et en Oncopharmacologie, Aix-Marseille Univ, Marseille, France.|Hematology and Pediatric Oncology Department, La Timone University Hospital of Marseille, Marseille, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: André
authors.affiliation: Department of Oncology, IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Via La Masa 19, 20156, Milan, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: D'Incalci
authors.affiliation: Clinica di Oncoematologia, Dipartimento di Pediatria, via Giustiniani 3, 35100, Padua, Italy.
authors.forename: Gianni
authors.initials: G
authors.lastname: Bisogno
authors.affiliation: Paediatric Haematology and Oncology, University Hospital Muenster, Albert-Schweitzer-Campus 1, Building A1, 48149, Münster, Germany. boosj@uni-muenster.de.
authors.forename: Joachim
authors.initials: J
authors.lastname: Boos
mesh_terms: D000293:Adolescent; D000903:Antibiotics, Antineoplastic / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000493:pharmacokinetics / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008954:Models, Biological; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D000903:Antibiotics, Antineoplastic; D004317:Doxorubicin