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A systematic literature analysis of correlative studies in low-dose metronomic chemotherapy trials

    Gemma Cramarossa

    Division of Medical Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Canada

    ,
    Esther K Lee

    Division of Medical Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Canada

    ,
    Lavarnan Sivanathan

    Division of Medical Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Canada

    Sunnybrook Research Institute, Biological Sciences Platform, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Canada

    ,
    Soley Georgsdottir

    Division of Medical Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Canada

    ,
    Kelly Lien

    Division of Medical Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Canada

    ,
    Keemo Delos Santos

    Division of Medical Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Canada

    ,
    Kelvin Chan

    Division of Medical Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Canada

    &
    Urban Emmenegger

    *Author for correspondence:

    E-mail Address: urban.emmenegger@sunnybrook.ca

    Division of Medical Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Canada

    Sunnybrook Research Institute, Biological Sciences Platform, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Canada

    Published Online:https://doi.org/10.2217/bmm.14.14

    Low-dose metronomic (LDM) chemotherapy is a beneficial and very well-tolerated form of chemotherapy utilization characterized by the frequent and uninterrupted administration of low doses of conventional chemotherapeutic agents over prolonged periods of time. While patients resistant to standard maximum tolerated dose (MTD) chemotherapy may still benefit from LDM chemotherapy, there is a lack of predictive markers of response to LDM chemotherapy. We searched the MEDLINE, EMBASE, CENTRAL and PubMed databases for correlative studies conducted as part of LDM chemotherapy trials in order to identify the most promising biomarker candidates. Given the antiangiogenic properties of LDM chemotherapy, angiogenesis-related biomarkers were most commonly studied. However, significant correlations between angiogenesis-related biomarkers and study end points were rare and variable, even so far as biomarkers correlating positively with an end point in some studies and negatively with the same end point in other studies. Pursuing biomarkers outside the angiogenesis field may be more promising.

    Papers of special note have been highlighted as: • of interest; •• of considerable interest

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