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Metformin might block prostate cancer progression

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It’s time for a clinical trial

The authors provide a convincing case for a causal interpretation ... [and] a compelling rationale for conducting a large-scale long-term randomized trial of metformin in men with clinically localized disease. The potential benefits of metformin could exceed those of existing drug therapies, particularly given its safety profile. Based on the strong evidence of this well-executed study, metformin ... may potentially be a safe and effective secondary prevention strategy for prostate cancer (J. Clin. Oncol. 2013 Aug 5 [doi: 10.1200/JCO.2013.50.7715]).

Interestingly, although postdiagnostic use of metformin was highly significant, the association of cumulative metformin use before prostate cancer diagnosis with prostate cancer death was null. As prostate cancer date of diagnosis is a rather arbitrary point in the progression of the disease, this discrepancy between the impact of pre- and postdiagnostic use is perplexing and warrants further study.

Kathryn Penney, Sc.D., is a medical epidemiologist at Brigham and Women’s Hospital in Boston. Dr. Meir Stampfer is professor of nutrition and epidemiology at Harvard Medical School, Boston. They reported no relevant conflicts of interest.


 

FROM THE JOURNAL OF CLINICAL ONCOLOGY

Metformin appears to have slowed, or perhaps even halted, the progression of prostate cancer in a retrospective, Canadian study of 3,837 diabetic men.

The study was published in the Journal of Clinical Oncology.

The longer the men were on the drug, the better they did; for each additional 6 months of treatment following diagnosis, prostate cancer mortality dropped 24% (adjusted hazard ratio 0.76). There was a 24% reduction in all-cause mortality in the first 6 months, as well (aHR, 0.76), but the association faded with time; 24-30 months out from diagnosis, metformin was associated with an all-cause mortality reduction of 7% (aHR, 0.93).

Although some of the men used other diabetes drugs such as sulfonylureas, thiazolidinediones, and insulin some of the time, only metformin improved prostate cancer outcomes, regardless of concomitant cancer treatments.

"We cannot conclude" that a nondiabetic population would see similar benefits, but the results "suggest that metformin may ... improve survival as an adjunct therapy, even among those already receiving optimal cancer treatments. We believe an interventional study of the use of metformin to delay progression in prostate cancer is warranted," wrote Dr. David Margel, a uro-oncology fellow at the University of Toronto when the study was conducted, and now a urologist at the Rabin Medical Center in Petah-Tikva, Israel (J. Clin. Oncol. 2013 Aug 5 [doi: 10.1200/JCO.2012.46.7043]).

Dr. Margel and his team are not the first to suggest that the ubiquitous diabetes drug might also be a potent cancer fighter. Metformin is being tested in dozens of trials not only for prostate tumors, but also for breast, brain, lung, uterine, colorectal, pancreatic, skin, blood, and thyroid cancers.

It probably doesn’t stop benign cells from turning cancerous, but may "influence cancer cells indirectly by decreasing insulin levels or directly by influencing cancer cell proliferation and apoptosis," the investigators wrote.

Study data came from health care databases kept by the province of Ontario, including the Ontario Cancer Registry and Ontario Diabetes Database.

The men were a median of 75 years old at diagnosis, and followed for a median of 4.64 years. About a quarter (976) presented with high-grade tumors, and almost 60% (2,167) with high-volume tumors. Thirty-five percent (1,343) died during the study period; prostate cancer was responsible for 7.6% (291) of the deaths.

"Overall, 1,251 (32.6%) and 1,619 (42.2%) were exposed to metformin before and after [prostate cancer] diagnosis, respectively. Patients were exposed to metformin for a median of 19 months before diagnosis and 8.9 months after diagnosis," Dr. Margel and his team noted.

The Ontario Ministry of Health and Long-Term Care funded the project. The authors have no conflicts of interest.

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