title: A systematic literature analysis of correlative studies in low-dose metronomic chemotherapy trials.
abstract: 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.
authors.affiliation: Division of Medical Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Canada.
authors.forename: Gemma
authors.initials: G
authors.lastname: Cramarossa
authors.forename: Esther K
authors.initials: EK
authors.lastname: Lee
authors.forename: Lavarnan
authors.initials: L
authors.lastname: Sivanathan
authors.forename: Soley
authors.initials: S
authors.lastname: Georgsdottir
authors.forename: Kelly
authors.initials: K
authors.lastname: Lien
authors.forename: Keemo Delos
authors.initials: KD
authors.lastname: Santos
authors.forename: Kelvin
authors.initials: K
authors.lastname: Chan
authors.forename: Urban
authors.initials: U
authors.lastname: Emmenegger
mesh_terms: D059250:Administration, Metronomic; D054316:Biomarkers, Pharmacological / Q000097:blood*; D006801:Humans; D016239:MEDLINE; D020714:Maximum Tolerated Dose
chemical_list: D054316:Biomarkers, Pharmacological
keywords: VEGF; angiogenesis; antiangiogenic therapy; biomarkers; cancer; low-dose metronomic chemotherapy; maximum tolerated dose chemotherapy; systematic literature analysis; thrombospondin-1