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PKPD and Disease Modeling: Concepts and Applications to Oncology

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Clinical Trial Simulations

Part of the book series: AAPS Advances in the Pharmaceutical Sciences Series ((AAPS,volume 1))

Abstract

Despite the transition from chemotherapy with cytotoxic and cytostatic drugs to targeted therapy with monoclonal antibodies, clinical decisions regarding the benefit of pharmacological interventions still rely on the concept of a maximum tolerated dose (MTD). In this chapter, it is shown that a model-based approach can be used in oncology to optimize dose selection and characterize drug effect on tumor growth, overall survival and safety. Furthermore, modeling and simulation also provides insight into the underlying mechanisms of action, enabling translation of the differences in pharmacology, safety and disease processes from preclinical experiments to clinical trials. A paradigm shift is proposed to bring the benefits of model-based drug development to cancer patients, in which biomarkers of safety and prognostic markers of overall survival are assessed to predict treatment outcome and disease progression.

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Authors and Affiliations

  1. Division of Pharmacology, Leiden-Amsterdam Center for Drug Research, Gorlaeus Laboratories, Einsteinweg 55, 2300, RA, Leiden, The Netherlands

    Oscar E. Della Pasqua

  2. Clinical Pharmacology & Discovery Medicine, GlaxoSmithKline R & D, 1-3 Ironbridge Road Stockley Park, UB11 1BT, Uxbridge, United Kingdom

    Oscar E. Della Pasqua

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Correspondence to Oscar E. Della Pasqua .

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Editors and Affiliations

  1. Department of Advanced Modeling & Simula, Janssen Research & Development, LLC, Route 202 S. 920, Raritan, 08869, New Jersey, USA

    Holly H. C. Kimko

  2. Dept. Biopharmaceutical Sciences, University of California, San Francisco, Parnassus Ave. 513, San Francisco, 94143-0446, California, USA

    Carl C. Peck

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Pasqua, O.E.D. (2011). PKPD and Disease Modeling: Concepts and Applications to Oncology. In: Kimko, H., Peck, C. (eds) Clinical Trial Simulations. AAPS Advances in the Pharmaceutical Sciences Series, vol 1. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-7415-0_13

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