Pre-surgical metformin In uterine malignancy (PREMIUM): a multi-center, randomized double-blind, placebo-controlled phase 3 trial
dc.contributor.author | Kitson, S | |
dc.contributor.author | Maskell, Z | |
dc.contributor.author | Sivalingam, Vanitha | |
dc.contributor.author | Allen, J | |
dc.contributor.author | Ali, S | |
dc.contributor.author | Burns, S | |
dc.contributor.author | Gilmour, K | |
dc.contributor.author | Latheef, R | |
dc.contributor.author | Slade, Richard J | |
dc.contributor.author | Pemberton, P | |
dc.contributor.author | Shaw, J | |
dc.contributor.author | Ryder, D | |
dc.contributor.author | Kitchener, H | |
dc.contributor.author | Crosbie, J | |
dc.date.accessioned | 2019-02-08T15:20:06Z | |
dc.date.available | 2019-02-08T15:20:06Z | |
dc.date.issued | 2018 | en |
dc.identifier.citation | Kitson 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.pmid | 30563932 | en |
dc.identifier.doi | 10.1158/1078-0432.CCR-18-3339 | en |
dc.identifier.uri | http://hdl.handle.net/10541/621504 | |
dc.description.abstract | Purpose 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.iso | en | en |
dc.relation.url | https://dx.doi.org/10.1158/1078-0432.CCR-18-3339 | en |
dc.title | Pre-surgical metformin In uterine malignancy (PREMIUM): a multi-center, randomized double-blind, placebo-controlled phase 3 trial | en |
dc.type | Article | en |
dc.contributor.department | Division of Cancer Sciences, University of Manchester | en |
dc.identifier.journal | Clincal Cancer Research | en |
dc.description.note | en] |