BERKELEY, CA (UroToday.com) - There is growing evidence that the biguanide, metformin, which is used to treat diabetes mellitus type 2, may have a place in the management of prostate cancer (PC). In 2013, data was published on the association of PC-specific and all-cause mortality and metformin exposure among diabetic men following the diagnosis of PC. However this was an observational study and the authors state that the true effect of metformin on PC can only be determined with a carefully designed, randomized, controlled study. In a retrospective analysis, metformin use in diabetic men was also independently associated with a decrease in the development of castration resistant PC (CRPC) compared with diabetic non-metformin patients. In our small phase II trial we could show a modest effect of metformin in some patients with progressive CRPC in terms of disease stabilization and prolongation of prostate-specific antigen doubling time as well as effects on metabolic parameters .
However, it is too early to recommend metformin to all men with PC. Efforts are underway to assess metformin in randomized trials. Both improvement of PC-specific endpoints, as well as prevention of metabolic sequelae of androgen deprivation therapy or novel androgen receptor inhibitors, would be meaningful to achieve. Many questions remain as to the optimal dose of metformin, possible combinations with other treatments, and whether other members of the class of biguanide drugs may have anticancer activity. The metformin story continues and might yet contain some “sweet tooth” surprises.
- Margel D, Urbach DR, Lipscombe LL, et al. Metformin use and all-cause and prostate cancer-specific mortality among men with diabetes. Journal of Clinical Oncology: official journal of the American Society of Clinical Oncology. 2013;31(25):3069-75. Epub 2013/08/07.
- Margel D, Urbach D, Fleshner N, Austin PC. Reply to m.m.j. Zanders et al. Journal of Clinical Oncology: official journal of the American Society of Clinical Oncology. 2014;32(7):702. Epub 2014/01/08.
- Spratt DE, Zhang C, Zumsteg ZS, Pei X, Zhang Z, Zelefsky MJ. Metformin and prostate cancer: reduced development of castration-resistant disease and prostate cancer mortality. European Urology. 2013;63(4):709-16. Epub 2013/01/05.
- Rothermundt C, Hayoz S, Templeton AJ, et al. Metformin in Chemotherapy-naive Castration-resistant Prostate Cancer: A Multicenter Phase 2 Trial (SAKK 08/09). European Urology. 2014. Epub 2014/01/15.
- Clyne M. Prostate cancer: Should we give metformin to all men with CRPC? Nature reviews Urology. 2014;11(2):63. Epub 2014/01/22.
- Smith M, Borre M, Rathenborg P, et al. Efficacy and safety of enzalutamide (ENZA) monotherapy in hormone-naive prostate cancer (HNPC). Journal of Clinical Oncology: official journal of the American Society of Clinical Oncology 2013 (suppl; abstr 5001).
- Azvolinsky A. Repurposing to fight cancer: the metformin-prostate cancer connection. Journal of the National Cancer Institute. 2014;106(2):dju030. Epub 2014/02/11.
- Mc Ewan I. Sweet Tooth. United Kingdom: Jonathan Cape; 2012.
Christian Rothermundt as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.
Cantonal Hospital St. Gallen, St. Gallen, Switzerland