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Defining the Starting Dose: Should It Be mg/kg, mg/m2, or Fixed?

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Handbook of Anticancer Pharmacokinetics and Pharmacodynamics

Part of the book series: Cancer Drug Discovery and Development ((CDD&D))

Abstract

Background: Traditional cytotoxic drugs are characterized by a narrow therapeutic window and significant interpatient variability in therapeutic and toxic effects. The new targeted therapies have a larger therapeutic window and some have different drug clearance mechanisms. Objective: To provide an insight into history, rationales, and limitations of current dosing methods in traditional cytotoxic drugs and new targeted therapies and to suggest a practical framework for dose calculation and a basis for future research and clinical studies. Methods: Review of relevant literature related to dose calculation of anticancer drugs. Results: Body surface area (BSA) or weight-based dosing and fixed dosing fail to standardize systemic anticancer drug exposure between individuals. Strategies using clinical parameters, genotype and phenotype markers, and therapeutic drug monitoring all have potential and each has a role for specific drugs. However, no one method is a practical dose calculation strategy for many or all drugs. Neither body size nor fixed dosing alone can be used for currently available drugs. Conclusion: Dosing strategies for anticancer drugs should be individualized according to elimination mechanisms and individual patient characteristics. Ways to determine these factors require further investigation and should be a component of early phase studies.

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Authors and Affiliations

  1. Department of Medical Oncology, University of Sydney, Westmead Hospital, Westmead, 2145, NSW, Australia

    Bo Gao & Howard Gurney

  2. Department of Medical Oncology F4-224, Academic Medical Center, 22660, 1100DD, Amsterdam, The Netherlands

    Heinz-Josef Klumpen

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  1. Bo Gao
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  2. Heinz-Josef Klumpen
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  3. Howard Gurney
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Correspondence to Howard Gurney .

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Editors and Affiliations

  1. Sidney Kimmel Comprehensive Cancer Cente, Baltimore, Maryland, USA

    Michelle A. Rudek

  2. Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA

    Cindy H. Chau

  3. Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA

    William D. Figg

  4. Moffitt Cancer Center, Tampa, Florida, USA

    Howard L. McLeod

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Gao, B., Klumpen, HJ., Gurney, H. (2014). Defining the Starting Dose: Should It Be mg/kg, mg/m2, or Fixed?. In: Rudek, M., Chau, C., Figg, W., McLeod, H. (eds) Handbook of Anticancer Pharmacokinetics and Pharmacodynamics. Cancer Drug Discovery and Development. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-9135-4_4

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