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Titel: Can we optimise doxorubicin treatment regimens for children with cancer? Pharmacokinetic simulations and a Delphi consensus procedure
VerfasserIn: Siebel, Christian
Würthwein, Gudrun
Lanvers-Kaminsky, Claudia
André, Nicolas
Berthold, Frank
Castelli, Ilaria
Chastagner, Pascal
Doz, François
English, Martin
Escherich, Gabriele
Frühwald, Michael C.
Graf, Norbert
Groll, Andreas H.
Ruggiero, Antonio
Hempel, Georg
Boos, Joachim
Sprache: Englisch
Titel: BMC Pharmacology & Toxicology
Bandnummer: 21
Heft: 1
Verlag/Plattform: BMC
Erscheinungsjahr: 2020
Freie Schlagwörter: Doxorubicin
Children
Cardiotoxicity
Pharmacokinetics
Delphi procedure
DDC-Sachgruppe: 610 Medizin, Gesundheit
Dokumenttyp: Journalartikel / Zeitschriftenartikel
Abstract: Background: Despite its cardiotoxicity doxorubicin is widely used for the treatment of paediatric malignancies. Current treatment regimens appear to be suboptimal as treatment strategies vary and do not follow a clear pharmacological rationale. Standardisation of dosing strategies in particular for infants and younger children is required but is hampered by scarcely defined exposure-response relationships. The aim is to provide a rational dosing concept allowing for a reduction of variability in systemic therapy intensity and subsequently unforeseen side effects. Methods: Doxorubicin plasma concentrations in paediatric cancer patients were simulated for different treatment schedules using a population pharmacokinetic model which considers age-dependent differences in doxorubicin clearance. Overall drug exposure and peak concentrations were assessed. Simulation results were used to support a three round Delphi consensus procedure with the aim to clarify the pharmacological goals of doxorubicin dosing in young children. A group of 28 experts representing paediatric trial groups and clinical centres were invited to participate in this process. Results: Pharmacokinetic simulations illustrated the substantial differences in therapy intensity associated with current dosing strategies. Consensus among the panel members was obtained on a standardised a priori dose adaptation that individualises doxorubicin doses based on age and body surface area targeting uniform drug exposure across children treated with the same protocol. Further, a reduction of peak concentrations in very young children by prolonged infusion was recommended. Conclusions: An approach to standardise current dose modification schemes in young children is proposed. The consented concept takes individual pharmacokinetic characteristics into account and involves adaptation of both the dose and the infusion duration potentially improving the safety of doxorubicin administration.
DOI der Erstveröffentlichung: 10.1186/s40360-020-00417-2
URL der Erstveröffentlichung: https://doi.org/10.1186/s40360-020-00417-2
Link zu diesem Datensatz: urn:nbn:de:bsz:291--ds-406338
hdl:20.500.11880/36505
http://dx.doi.org/10.22028/D291-40633
ISSN: 2050-6511
Datum des Eintrags: 28-Sep-2023
Bezeichnung des in Beziehung stehenden Objekts: Supplementary information
In Beziehung stehendes Objekt: https://static-content.springer.com/esm/art%3A10.1186%2Fs40360-020-00417-2/MediaObjects/40360_2020_417_MOESM1_ESM.docx
https://static-content.springer.com/esm/art%3A10.1186%2Fs40360-020-00417-2/MediaObjects/40360_2020_417_MOESM2_ESM.pdf
https://static-content.springer.com/esm/art%3A10.1186%2Fs40360-020-00417-2/MediaObjects/40360_2020_417_MOESM3_ESM.docx
https://static-content.springer.com/esm/art%3A10.1186%2Fs40360-020-00417-2/MediaObjects/40360_2020_417_MOESM4_ESM.docx
Fakultät: M - Medizinische Fakultät
Fachrichtung: M - Pädiatrie
Professur: M - Prof. Dr. Norbert Graf
Sammlung:SciDok - Der Wissenschaftsserver der Universität des Saarlandes

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Diese Ressource wurde unter folgender Copyright-Bestimmung veröffentlicht: Lizenz von Creative Commons Creative Commons