ArticleBMC pharmacology & toxicology2020
Can we optimise doxorubicin treatment regimens for children with cancer? Pharmacokinetic simulations and a Delphi consensus procedure.
Article in BMC pharmacology & toxicology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.
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Who cites it
10 citing papers in PubMed, 1 synthesis or guideline pooled it, 18 citations in OpenAlex.
- Clinical pharmacology of cytotoxic drugs in neonates and infants: Providing evidence-based dosing guidance.European journal of cancer (Oxford, England : 1990) · 2022Pooled it
- The effects of doxorubicin on blood-brain barrier integrity in hCMEC/D3.Neurotoxicology · 2025Article
- A Population Pharmacokinetic Study to Evaluate Doxorubicin Exposure Across All Age Groups.Clinical pharmacokinetics · 2024Article
- CD8Nature cardiovascular research · 2024Article
- Comparison of bolus administration and short-term infusion versus long-term infusion of doxorubicin in terms of cardiotoxicity and efficacy.Naunyn-Schmiedeberg's archives of pharmacology · 2024Review
- Cardiotoxicity of CPX-351 in children and adolescents with relapsed AML: a Children's Oncology Group report.Frontiers in cardiovascular medicine · 2024Article
- Mitigation of Cardiovascular Disease and Toxicity through NRF2 Signalling.International journal of molecular sciences · 2023Review
- Dormant SOX9-Positive Cells Facilitate MYC-Driven Recurrence of Medulloblastoma.Cancer research · 2022Article
- Isorhamnetin: a flavonoid, attenuated doxorubicin-induced testicular injury via regulation of steroidogenic enzymes and apoptotic signaling gene expression in male rats.Toxicology research · 2022Article
- Bioanalysis of doxorubicin aglycone metabolites in human plasma samples-implications for doxorubicin drug monitoring.Scientific reports · 2020Article
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Authors and funding
16 authors at 10 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundDespite 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.
methodsDoxorubicin 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.
resultsPharmacokinetic 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.
conclusionsAn 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.
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