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Optimized Dosing: The Next Step in Precision Medicine in Non-Small-Cell Lung Cancer

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Abstract

In oncology, and especially in the treatment of non-small-cell lung cancer (NSCLC), dose optimization is often a neglected part of precision medicine. Many drugs are still being administered in “one dose fits all” regimens or based on parameters that are often only minor determinants for systemic exposure. These dosing approaches often introduce additional pharmacokinetic variability and do not add to treatment outcomes. Fortunately, pharmacological knowledge is increasing, providing valuable information regarding the potential of, for example, therapeutic drug monitoring. This article focuses on the evidence for the most promising and easily implemented optimized dosing approaches for the small-molecule inhibitors, chemotherapeutic agents, and monoclonal antibodies as treatment options currently approved for NSCLC. Despite limitations such as investigations having been conducted in oncological diseases other than NSCLC or the retrospective origin of many analyses, an alternative dosing regimen could be beneficial for treatment outcomes, prescriber convenience, or financial burden on healthcare systems. This review of the literature provides recommendations on the implementation of dose optimization and advice regarding promising strategies that deserve further research in NSCLC.

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Authors and Affiliations

  1. Department of Pharmacy and Pharmacology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands

    René J. Boosman, Jos H. Beijnen & Alwin D. R. Huitema

  2. Department of Thoracic Oncology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek, Amsterdam, The Netherlands

    Jacobus A. Burgers & Egbert F. Smit

  3. Department of Medical Oncology and Clinical Pharmacology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek, Amsterdam, The Netherlands

    Neeltje Steeghs

  4. Department of Pulmonary Diseases, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands

    Anthonie J. van der Wekken

  5. Department of Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands

    Jos H. Beijnen

  6. Department of Pharmacology Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands

    Alwin D. R. Huitema

  7. Department of Clinical Pharmacy, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands

    Alwin D. R. Huitema

  8. Department of Pharmacy, Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands

    Rob ter Heine

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  1. René J. Boosman
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Correspondence to René J. Boosman.

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Conflict of interest

RJ Boosman, EF Smit, ADR Huitema, and R ter Heine have no conflicts of interest that might be relevant to the contents of this manuscript. JA Burgers is a member of advisory boards for Roche and BMS and has received support from MSD for an investigator-initiated study. All of these conflicts are outside of the submitted work, and any reimbursement was paid to their institution. N Steeghs has provided consultation or attended advisory boards for AIMM Therapeutics, Boehringer Ingelheim, and Ellipses Pharma; has received research grants for the institute from AB Science, Abbvie, Actuate Therapeutics, Amgen, Array, AstraZeneca/MedImmune, Bayer, Blueprint Medicines, Boehringer Ingelheim, Bristol-Myers Squibb, Cantargia, CellCentric, Cytovation, Deciphera, Genentech/Roche, GlaxoSmithKline, Incyte, Lilly, Merck Sharp & Dohme, Merus, Molecular Partners, Novartis, Pfizer, Pierre Fabre, Roche, Sanofi, Taiho, and Takeda. All of these conflicts are outside of the submitted work, and any reimbursement was paid to their institution. AJ van der Wekken has received grants from AstraZeneca, Boehringer Ingelheim, Pfizer, Roche, and Takeda; has received payment for lectures from Pfizer, Boehringer Ingelheim, and Takeda; and is a member of the advisory boards of Boehringer Ingelheim, Takeda, and Janssen. All of these are outside of the submitted work. JH Beijnen has received payment for expert testimony for Hoyng Tokh Monegier (paid to their institution), is a part-time employee and (in)direct stockholder of Modra Pharmaceuticals and (jointly) holds a patent on oral taxane formulations clinically developed by Modra Pharmaceuticals. Modra Pharmaceuticals is a small spin-off company of the Netherlands Cancer Institute. All of these conflicts are outside of the submitted work.

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Authors’ contributions

RJ Boosman: conceptualization, methodology, investigation, writing original draft. JA Burgers, EF Smit, N Steeghs: conceptualization, methodology, writing review and editing. AJ van der Wekken: writing review and editing. JH Beijnen: writing review and editing. ADR Huitema: conceptualization, methodology, writing review and editing, supervision. R ter Heine: conceptualization, methodology, writing review and editing, and supervision.

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Boosman, R.J., Burgers, J.A., Smit, E.F. et al. Optimized Dosing: The Next Step in Precision Medicine in Non-Small-Cell Lung Cancer. Drugs 82, 15–32 (2022). https://doi.org/10.1007/s40265-021-01654-3

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