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Therapeutic Drug Monitoring of Targeted Anticancer Therapy. Tyrosine Kinase Inhibitors and Selective Estrogen Receptor Modulators: A Clinical Pharmacology Laboratory Perspective

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Abstract

In the last decade, a new era of cancer therapy has emerged, and the treatment of several cancers has shifted from cytotoxic and nonspecific chemotherapy to chronic oral treatment with targeted molecular therapies. Most oral anticancer-targeted drugs approved at present are tyrosine kinase inhibitors (TKIs) and some of them are accompanied with diagnostic test aiming at preselecting patients who are more likely to respond to anticancer treatment, constituting vivid examples of the emerging field of personalized medicine. In that context, since most TKIs are also characterized by an important interindividual variability in their pharmacokinetics, renewed efforts for treatment optimization should be made for targeting adequate drug exposure in patients, increasing thereby the likelihood of optimal clinical response and tolerability of anticancer treatment. This can be done through the Therapeutic Drug Monitoring (TDM) approach, whereby the careful selection of TKI dosage is adapted to each patient according to individual plasma levels, contributing to minimize the risk of major adverse reactions and to increase the probability of efficient, long-lasting, therapeutic response. This chapter reviews the bioanalytical developments by chromatography and mass spectrometry in the field of targeted anticancer therapy, across the growing family of recent FDA-approved oral TKIs as well as for tamoxifen and its active metabolites, being in fact the most widely used targeted anticancer agent. The text also provides an introduction to existing pharmacokinetics–pharmacodynamics knowledge in the field of targeted anticancer therapy, and the rationale for a TDM program for TKIs.

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Acknowledgments

This chapter has been realized within the frame of the research project “Integrative cellular pharmacokinetics/pharmacodynamics/pharmacoproteomics studies of anticancer TKIs in leukemia” (SNF grant no. 310030_138097/1 to LAD) supported by the Swiss National Science Foundation (SNF, Switzerland). It also benefited from the support of the SNF-funded initiative Nano-Tera (ISyPeM project [269] to TB).

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  1. Innovation and Development Unit, Service of Biomedicine, University Hospital Center and University of Lausanne, Laboratory BH 18-218, Center Hospitalier Universitaire Vaudois, CHUV, 1011, Lausanne, Switzerland

    Laurent Decosterd

  2. Division of Clinical Pharmacology, Service of Biomedicine, University Hospital Center and University of Lausanne, Lausanne & School of Pharmaceutical Sciences, University of Geneva and Lausanne, Geneva, Switzerland

    Elyes Dahmane & Chantal Csajka

  3. Innovation and Development Unit, Division of Clinical Pharmacology, Service of Biomedicine, University Hospital Center and University of Lausanne, Lausanne & School of Pharmaceutical Sciences, University of Geneva and Lausanne, Geneva, Switzerland

    Marine Neeman & Amina Haouala

  4. Division of clinical Pharmacology, Service of Biomedicine, University Hospital Center and University of Lausanne, Lausanne, Switzerland

    Thierry Buclin & Nicolas Widmer

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    Q. Alan Xu

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    Timothy L. Madden

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Decosterd, L. et al. (2012). Therapeutic Drug Monitoring of Targeted Anticancer Therapy. Tyrosine Kinase Inhibitors and Selective Estrogen Receptor Modulators: A Clinical Pharmacology Laboratory Perspective. In: Xu, Q., Madden, T. (eds) LC-MS in Drug Bioanalysis. Springer, Boston, MA. https://doi.org/10.1007/978-1-4614-3828-1_9

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