Международный эндокринологический журнал 5 (53) 2013

Diabetic men with prostate cancer (PC) had a 24% decreased risk for PC-specific death for each additional 6 months of metformin treatment after cancer diagnosis, David Margel, MD, PhD, and colleagues reported online August 5 in the Journal of Clinical Oncology (2013). Cumulative metformin use was also associated with decreased risk for all-cause mortality for the first 6 months after diagnosis.

«This study adds to the growing body of evidence that prostate cancer may be a metabolic malignancy. More and more evidence is demonstrating that prostate cancer progression may be affected by obesity, metabolic syndrome, and diabetes», Dr. Margel, who is from the Division of Urology at the University of Toronto, Ontario, Canada, told Medscape Medical News.

«Metformin is safe, has minimal side effects, and is cheap. Therefore, it may be ideal as a secondary prevention strategy even among nondiabetic men with PC. We believe our study sets the foundation for such a study of metformin in PC», Dr. Margel said. However, he emphasized that currently, metformin should be used only in accordance with current guidelines for diabetes treatment.

The researchers conducted a population-based retrospective cohort study to examine the association between cumulative duration of metformin use after PC diagnosis and all-cause and PC-specific mortality in men with diabetes. The cohort included 3837 diabetes patients older than 66 years from several Ontario healthcare administrative databases who subsequently developed PC. Median follow-up was 4.64 years (range 2.7 to 7.1 years), during which 35 % of patients died, including 7.6 % who died as a result of PC.

The investigators found that the adjusted hazard ratio (HR) for PC-specific mortality was 0.76 for each additional 6 months of metformin use. In addition, the HR for all-cause mortality declined over time from an HR of 0.76 in the first 6 months to 0.93 between 24 and 30 months. No other antidiabetic drugs affected either PC-specific or all-cause mortality.

The metformin benefit occurred regardless of cancer treatment regimen. «These results suggest that metformin may further improve survival as an adjunct therapy, even among those already receiving optimal cancer treatments», the authors wrote.

Dr. Margel and colleagues warned against overinterpretation of their data. «Finally, because our cohort was limited to patients with diabetes, we cannot conclude whether similar effects of metformin would be seen in a nondiabetic population. Thus, our study results do not demonstrate a survival benefit for diabetic men who use metformin compared with men who do not have diabetes», they wrote.

«This is an interesting publication that adds to a rapidly growing body of literature (composed mainly of retrospective studies) which has raised the hypothesis that metformin may have anticancer activity. This is a very interesting hypothesis that deserves examination in carefully designed, prospective clinical trials. Retrospective studies are well known to be affected by confounding factors, so only prospective studies in well-defined clinical settings can answer these important questions», oncologist and endocrinologist Nicholas Mitsiades, MD, PhD, told Medscape Medical News. Dr. Mitsiades, who is assistant professor, Departments of Medicine and Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas, was not involved in the study.

Dr. Mitsiades said that key unanswered questions include whether metformin has true anticancer activity, whether the results in the retrospective studies were influenced by potential differences between patients treated with metformin and those treated with insulin/sulfonylureas, and whether the anticancer activity occurs only in patients with diabetes or other metabolic abnormalities.

«Although metformin is generally a safe drug, I would not prescribe it off-label for treatment of cancer in a patient who has normal glucose metabolism», Dr. Mitsiades said.

He added that clinicians should put more emphasis on a healthy, low-fat diet and daily exercise, which have been shown in prospective studies to significantly improve clinical outcomes in several types of cancer, including PC.