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Pharmacokinetics and Pharmacogenetics of Metronomics

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Abstract

Over the last 15 years, metronomic chemotherapy (MC) has been undergoing major evolution since its initial description as an antiangiogenic therapy. The discovery of both its proimmune and direct anticancer effects has led to the acceptance of its intrinsic multi-targeted properties. MC is frequently combined in the clinic with drug repositioning (DR), which consists of using non-anticancer drugs for which their anticancer properties have been described. Metronomics has been defined as the combination of MC and DR and paves the way for both broadening and/or fine-tuning the potential of MC. Despite the many clinical studies conducted on metronomic chemotherapy in the past 15 years, there is a lack of pharmacokinetic and pharmacogenetics data. Indeed, only the pharmacokinetics of anticancer agents given in a metronomic manner, such as vinorelbine, irinotecan, and UFT, has been reported, but surprisingly no data are available on the most commonly used agents like capecitabine or cyclophosphamide. Moreover, few data are available on the pharmacogenetics of metronomic chemotherapy, to what extent genetics can impact on pharmacokinetics and, in turn, affect pharmacodynamics. Trials integrating pharmacokinetic and pharmacogenetics research are necessary to better evaluate the clinical benefit of MC and represent a mandatory step to treatment personalization.

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Authors and Affiliations

  1. Department of Pediatric Hematology and Oncology, AP-HM, La Timone Hospital, 264 rue Saint-Pierre, Marseille, 13005, France

    Nicolas André & Marie Amélie Heng

  2. UMR S_911 CRO2 Aix Marseille Université, Marseille, France

    Nicolas André & Eddy Pasquier

  3. Centre d’Essais Précoce Cancérologie Marseille (CEPCM), Hospital of La Timone, AP-HM, Marseille, 13005, France

    Nicolas André

  4. Metronomics Global Heath Initiative, Marseille, France

    Nicolas André & Eddy Pasquier

  5. SMARTc Aix Marseille Université, Inserm, CRO2 UMR_S 911, Marseille, 13005, France

    Joseph Ciccolini

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  1. Nicolas André
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  2. Joseph Ciccolini
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  3. Marie Amélie Heng
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  4. Eddy Pasquier
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Correspondence to Nicolas André .

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Editors and Affiliations

  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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André, N., Ciccolini, J., Heng, M.A., Pasquier, E. (2016). Pharmacokinetics and Pharmacogenetics of Metronomics. In: Bonate, P., Howard, D. (eds) Pharmacokinetics in Drug Development. Springer, Cham. https://doi.org/10.1007/978-3-319-39053-6_10

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