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Controversies in Oncology: Size Based vs. Fixed Dosing

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Pharmacokinetics in Drug Development

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Abstract

To find the right dose and regimen is crucial for the therapeutic effectiveness of oncolytics. Prior to the 1960s, early oncologists dosed their patients at the maximum tolerated dose (MTD) using either fixed doses (sometimes called flat doses) or doses standardized to total body weight (TBW). In the 1960s, this changed as oncology dosing switched to the MTD expressed per patient body surface area (mg/m2), because it was shown that, expressed in this manner, the MTD was approximately the same in humans as in animal species. This remained for decades until in the 1990s when molecularly targeted therapeutics and monoclonal antibodies began to be introduced into clinical practice, and it was no longer necessary to dose patients at the MTD. Further, pharmacokineticists started to realize that using size-based dosing did not reduce interpatient variability for many drugs. Today, the dose regimen developed for new anticancer drugs can be fixed dose, BSA dosed, or TBW dosed. The choice is rigorously evaluated based on sound scientific practice in confirmed in clinical trials. The purpose of this chapter is to discuss the history regarding size-based dosing and current practices for getting “the right dose” in oncology.

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Authors and Affiliations

  1. Pharmacokinetics/Modeling/Simulation 2N.184 Astellas, Global Clinical Pharmacology and Exploratory Development, 1 Astellas Way, Northbrook, IL, 60062, USA

    Peter L. Bonate Ph.D.

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  1. Peter L. Bonate Ph.D.
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Correspondence to Peter L. Bonate Ph.D. .

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  1. Pharmacokinetics/Modeling/Simulation 2N.184 Astellas, Global Clinical Pharmacology and Exploratory Development, Northbrook, Illinois, USA

    Peter L. Bonate

  2. Oncology Clinical Pharmacology Novartis, East Hanover, New Jersey, USA

    Danny R. Howard

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Bonate, P.L. (2016). Controversies in Oncology: Size Based vs. Fixed Dosing. In: Bonate, P., Howard, D. (eds) Pharmacokinetics in Drug Development. Springer, Cham. https://doi.org/10.1007/978-3-319-39053-6_4

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