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doi:10.22028/D291-40633
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 |
Dateien zu diesem Datensatz:
Datei | Beschreibung | Größe | Format | |
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s40360-020-00417-2.pdf | 934,82 kB | Adobe PDF | Öffnen/Anzeigen |
Diese Ressource wurde unter folgender Copyright-Bestimmung veröffentlicht: Lizenz von Creative Commons