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From Prospective Evaluation to Practice: Model-Informed Dose Optimization in Oncology

Bram C Agema1,2, Birgit C P Koch3,4, Ron H J Mathijssen5

  • 1Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University Medical Center, Dr. Molewaterplein 40, 3015 GD, Rotterdam, The Netherlands. b.agema@erasmusmc.nl.

Drugs
|February 12, 2025
PubMed

Insights

Model-informed precision dosing tailors cancer drug treatments to individual patients. While not yet standard, studies show it improves outcomes and reduces toxicity for certain oncology drugs, highlighting its future clinical value.

Area of Science:

  • Oncology
  • Pharmacokinetics
  • Clinical Pharmacology

Background:

  • Individual variability in drug response necessitates personalized dosing strategies in oncology.
  • Current dosing regimens for oncolytic drugs often lead to side effects and treatment failures.
  • Model-informed precision dosing (MIPD) offers a promising approach to optimize cancer therapy.

Purpose of the Study:

  • To provide a clinical perspective on model-informed precision dosing in oncology.
  • To review prospective implementation and validation studies of MIPD in cancer treatment.
  • To assess the current status and future potential of MIPD in clinical oncology.

Main Methods:

  • Literature review of prospective studies on model-informed precision dosing in oncology.
  • Identification of drugs with implemented or validated MIPD protocols.
  • Analysis of study outcomes focusing on drug exposure, variability, clinical efficacy, and toxicity.

Main Results:

  • Sixteen drugs were identified with prospective MIPD validation/implementation studies.
  • Improved clinical outcomes were observed for busulfan and high-dose methotrexate with MIPD.
  • Reduced toxicities were noted for busulfan and cyclophosphamide treatments.
  • Carboplatin dosing via the Calvert formula, a form of MIPD, did not require further outcome validation due to its established therapeutic window.

Conclusions:

  • Model-informed precision dosing demonstrates added value in oncology.
  • MIPD has the potential to significantly alter future cancer drug dosing regimens.
  • Further integration of MIPD into routine clinical practice is anticipated.

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