Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

Metformin and longevity (METAL): A window of opportunity study investigating the biological effects of metformin in localised prostate cancer

Date

09 Oct 2016

Session

Poster display

Presenters

Danielle Crawley

Citation

Annals of Oncology (2016) 27 (6): 243-265. 10.1093/annonc/mdw372

Authors

D. Crawley1, A. Chandra2, M. Loda3, C. Gillett4, P. Cathcart5, B. Challacombe5, G. Cook6, D. Cahill7, F. Cahill1, A. Santa Olalla1, G. George1, S. Rudman8, M. van Hemelrijck1

Author affiliations

  • 1 Research Oncology, King's College London Guy's Hospital, SE1 9RT - London/GB
  • 2 Histopathology, Guy's and St. Thomas' Hospital NHS Trust, SE1 9RT - London/GB
  • 3 Molecular Pathology, Dana-Farber Cancer Institute, Boston/US
  • 4 Division Of Cancer Studies, King's College London Guy's Hospital, SE1 9RT - London/GB
  • 5 Urology, Guy's and St. Thomas' Hospital NHS Trust, SE1 9RT - London/GB
  • 6 Nuclear Medicine, Guy's and St. Thomas' Hospital NHS Trust, SE1 9RT - London/GB
  • 7 Urology, Royal Marsden Hospital NHS Foundation Trust, London/GB
  • 8 Medical Oncology, Guy's and St. Thomas' Hospital NHS Trust, SE1 9RT - London/GB
More

Resources

Abstract 1847

Background

Metformin (1,1-dimethylbiguanide hydrochloride) is a biguanide oral hypoglycaemic agent commonly used for the treatment of type 2 diabetes mellitus. In addition to it's anti-diabetic effect, metformin has also been associated with a reduced risk of cancer incidence of a number of solid tumour including prostate cancer (PCa). However, the underlying biological mechanisms for these observations have not been fully characterised in PCa. One hypothesis is that the indirect insulin lowering effect may have an anti-neoplastic effect as elevated insulin and insulin like growth factor -1 (IGF-1) levels play a role in PCa development and progression. In addition, metformin is a potent activator of activated protein kinase (AMPK) which in turn inhibits the mammalian target of rapamycin (mTOR) and other signal transduction mechanisms . These direct effects can lead to reduced cell proliferation. Given its wide availability and tolerable side effect profile, metformin represents an attractive potential therapeutic option for men with PCa. Hence, the need for a clinical trial investigating its biological mechanisms in PCa.

Trial design

METAL is a multi-centre, randomized, placebo-controlled, double-blind, window of opportunity study investigating the biological mechanism of metformin in prostate cancer. 180 patients with newly-diagnosed, localised PCa scheduled for radical prostatectomy will be randomised 1:1 to receive metformin (1g bd) or placebo for four weeks (+/- 1 week) prior to prostatectomy. Tissue will be collected from both diagnostic biopsy and prostatectomy specimens. The primary endpoint is the difference in expression levels of markers of the FASN/AMPK pathway pre and post treatment between the placebo and metformin arms. Secondary endpoints include the difference in expression levels of indicators of proliferation (ki67 and TUNEL) pre and post treatment between the placebo and metformin arms. METAL is currently open to recruitment at Guy's and St Thomas' Hospital and the Royal Marsden Hospital, London.

Clinical trial identification

EudraCT 2014-005193-11

Legal entity responsible for the study

Co sponsored by King's College London and Guy's and St Thomas NHS Trust

Funding

JP Moulton Charitable Foundation

Disclosure

All authors have declared no conflicts of interest.

Resources from the same session

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings