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dc.contributor.authorKitson, S
dc.contributor.authorMaskell, Z
dc.contributor.authorSivalingam, Vanitha
dc.contributor.authorAllen, J
dc.contributor.authorAli, S
dc.contributor.authorBurns, S
dc.contributor.authorGilmour, K
dc.contributor.authorLatheef, R
dc.contributor.authorSlade, Richard J
dc.contributor.authorPemberton, P
dc.contributor.authorShaw, J
dc.contributor.authorRyder, D
dc.contributor.authorKitchener, H
dc.contributor.authorCrosbie, J
dc.date.accessioned2019-02-08T15:20:06Z
dc.date.available2019-02-08T15:20:06Z
dc.date.issued2018en
dc.identifier.citationKitson S, Maskell Z, Sivalingam VN, Allen JL, Ali S, Burns S, et al. Pre-surgical metformin In uterine malignancy (PREMIUM): a multi-center, randomized double-blind, placebo-controlled phase 3 trial. Clin Cancer Res. 2018 Dec 18.en
dc.identifier.pmid30563932en
dc.identifier.doi10.1158/1078-0432.CCR-18-3339en
dc.identifier.urihttp://hdl.handle.net/10541/621504
dc.description.abstractPurpose Endometrioid endometrial cancer is strongly associated with obesity and insulin resistance. Metformin, an insulin sensitizer, reduces endometrial tumor growth in vitro. Pre-surgical window studies allow rapid in vivo assessment of anti-tumor activity. Previous window studies found metformin reduced endometrial cancer proliferation but these lacked methodological rigor. PREMIUM measured the anti-proliferative effect of metformin in vivo using a robust window study design. PATIENTS AND METHODS: A multicenter, double-blind, placebo-controlled trial randomized women with atypical hyperplasia or endometrioid endometrial cancer to receive metformin (850mg daily for three days, and twice daily thereafter) or placebo for 1-5 weeks until surgery. The primary outcome was post-treatment immunohistochemical expression of Ki-67. Secondary outcomes investigated the effect of metformin on markers of the PI3K-Akt-mTOR and insulin signaling pathways and obesity. RESULTS: Eighty-eight women received metformin (n=45) or placebo (n=43) and completed treatment. There was no overall difference in post-treatment Ki-67 between the metformin and placebo arms, in an ANCOVA analysis adjusting for baseline Ki-67 expression (mean difference -0.57%, 95% CI -7.57%, 6.42%, p=0.87). Metformin did not affect expression of markers of the PI3K-Akt-mTOR or insulin signaling pathways, and did not result in weight loss. CONCLUSIONS: Short-term treatment with standard diabetic doses of metformin does not reduce tumor proliferation in women with endometrioid endometrial cancer awaiting hysterectomy. This study does not support a biological effect of metformin in endometrial cancer and casts doubt on its potential application in the primary and adjuvant treatment settings.en
dc.language.isoenen
dc.relation.urlhttps://dx.doi.org/10.1158/1078-0432.CCR-18-3339en
dc.titlePre-surgical metformin In uterine malignancy (PREMIUM): a multi-center, randomized double-blind, placebo-controlled phase 3 trialen
dc.typeArticleen
dc.contributor.departmentDivision of Cancer Sciences, University of Manchesteren
dc.identifier.journalClincal Cancer Researchen
dc.description.noteen]


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