Precision Dosing of Targeted Therapies Is Ready for Prime Time.


Journal

Clinical cancer research : an official journal of the American Association for Cancer Research
ISSN: 1557-3265
Titre abrégé: Clin Cancer Res
Pays: United States
ID NLM: 9502500

Informations de publication

Date de publication:
15 12 2021
Historique:
received: 23 11 2020
revised: 19 02 2021
accepted: 13 09 2021
pubmed: 23 9 2021
medline: 8 4 2022
entrez: 22 9 2021
Statut: ppublish

Résumé

Fixed dosing of oral targeted therapies is inadequate in the era of precision medicine. Personalized dosing, based on pharmacokinetic (PK) exposure, known as therapeutic drug monitoring (TDM), is rational and supported by increasing evidence. The purpose of this perspective is to discuss whether randomized studies are needed to confirm the clinical value of precision dosing in oncology. PK-based dose adjustments are routinely made for many drugs and are recommended by health authorities, for example, for patients with renal impairment or for drug-drug interaction management strategies. Personalized dosing simply extrapolates this paradigm from selected patient populations to each individual patient with suboptimal exposure, irrespective of the underlying cause. If it has been demonstrated that exposure is related to a relevant clinical outcome, such as efficacy or toxicity, and that exposure can be optimized by PK-guided dosing, it could be logically assumed that PK-guided dosing would result in better treatment outcomes without the need for randomized confirmatory trials. We propose a path forward to demonstrate the clinical relevance of individualized dosing of molecularly-targeted anticancer drugs.

Identifiants

pubmed: 34548319
pii: 1078-0432.CCR-20-4555
doi: 10.1158/1078-0432.CCR-20-4555
pmc: PMC8934568
mid: NIHMS1784075
doi:

Types de publication

Journal Article Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

6644-6652

Subventions

Organisme : NCI NIH HHS
ID : P30 CA047904
Pays : United States
Organisme : NCI NIH HHS
ID : U24 CA247643
Pays : United States
Organisme : NCI NIH HHS
ID : U24 CA247648
Pays : United States
Organisme : NCI NIH HHS
ID : UM1 CA186690
Pays : United States

Informations de copyright

©2021 American Association for Cancer Research.

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Auteurs

Stefanie L Groenland (SL)

Department of Clinical Pharmacology, Division of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, the Netherlands.

Remy B Verheijen (RB)

Department of Pharmacy & Pharmacology, The Netherlands Cancer Institute, Amsterdam, the Netherlands.

Markus Joerger (M)

Department of Medical Oncology and Hematology, Cantonal Hospital, St. Gallen, Switzerland.

Ron H J Mathijssen (RHJ)

Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands.

Alex Sparreboom (A)

Division of Pharmaceutics and Pharmacology, College of Pharmacy and Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio.

Jos H Beijnen (JH)

Department of Pharmacy & Pharmacology, The Netherlands Cancer Institute, Amsterdam, the Netherlands.
Department of Pharmaceutical Sciences, Utrecht University, Utrecht, the Netherlands.

Jan H Beumer (JH)

Cancer Therapeutics Program, UPMC Hillman Cancer Center, Pittsburgh, Pennsylvania.

Neeltje Steeghs (N)

Department of Clinical Pharmacology, Division of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, the Netherlands.

Alwin D R Huitema (ADR)

Department of Pharmacy & Pharmacology, The Netherlands Cancer Institute, Amsterdam, the Netherlands. a.huitema@nki.nl.
Department of Clinical Pharmacy, Utrecht University Medical Center, Utrecht, the Netherlands.
Department of Pharmacology, Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands.

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