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Mechanisms of Action of Low-Dose Metronomic Chemotherapy

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Metronomic Chemotherapy

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Abstract

Evidence from a growing body of preclinical and clinical studies points to the efficacy of continuously administrating anticancer chemotherapeutic drugs in low doses. This relatively new treatment strategy concept is called low-dose metronomic (LDM) chemotherapy. The therapeutic efficacy of LDM has been assessed for reducing the tumor load during the acute phase and in delaying relapse during the maintenance phase. The major benefits found in using LDM include the lack of major toxicities or complications as compared to conventional chemotherapy regimens and improved quality of life. Traditional therapeutic modalities in oncology aim toward more specific tumor targets at the tumor microenvironment, whereas LDM chemotherapy acts on a broad spectrum of mechanisms, some of which are still not clear. We will discuss in this chapter several possible LDM chemotherapy anticancer mechanisms of action. Initially, LDM was considered an antiangiogenic treatment strategy; however, in the last decade additional preclinical studies uncovered other possible mechanisms including enhancing the antitumor immune response, substantially increasing the efficacy of targeted drugs by various mechanisms, targeting a subset of chemotherapy-resistant tumor cells, and blunting host response effects found following conventional therapy. While LDM chemotherapy is currently undergoing phase III clinical evaluation, its mechanisms of action are only partially understood. Elucidating LDM’s mechanisms of action will give physicians an additional major weapon to deploy in the comprehensive management of cancer.

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Acknowledgments

This study was supported in part by the European Research Council (under FP-7 program) and Israel Cancer Research Fund to YS. The authors would like to thank Prof. Giulio Francia for the critical reading of this chapter. The authors disclose no conflict of interest.

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  1. Department of Molecular Pharmacology, Rappaport Faculty of Medicine, Technion – Israel Institute of Technology, 1 Efron St. Bat Galim, Haifa, 31096, Israel

    Ella Fremder & Yuval Shaked PhD

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  1. Ella Fremder
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  2. Yuval Shaked PhD
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Correspondence to Yuval Shaked PhD .

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Editors and Affiliations

  1. Division of Pharmacology, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy

    Guido Bocci

  2. Department of Biological Sciences, University of Texas at El Paso, El Paso, Texas, USA

    Giulio Francia

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Fremder, E., Shaked, Y. (2014). Mechanisms of Action of Low-Dose Metronomic Chemotherapy. In: Bocci, G., Francia, G. (eds) Metronomic Chemotherapy. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-43604-2_2

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