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An anti-diabetic drug to fight cancer? Metformin use associated with greater survival in Ovarian Ca

22 April 2013

Today I came across a very interesting case-control study by Kumar et al. on the effects of metformin on the outcomes of ovarian cancer patients.

This study piqued my interest for a couple reasons. Metformin is already used in the clinic, is widely available, inexpensive, and its side effects are well-documented. It is taken orally, not intravienously, which makes administration less stressful for patients. Existing drugs that can be re-purposed as anti-cancer drugs are of great interest for another reason: time and money. If Yours Truly identified the achilles heel of all cancer tomorrow (a highly unlikely event) developing a drug to exploit this hole in the armor might take as long as 10-17 years and cost upwards of $800 million to develop and test a new drug (source).

There is also the phenomenon of physicians being hesitant to prescribe new therapies or drugs that they are unfamiliar with. A re-purposed drug might get quicker recognition and use in the clinic than a brand new drug.

I guess what I’m trying to say is that if a drug like metformin could be re-purposed to fight cancer, it would have immediate clinical impact treating a very, very nasty disease: ovarian cancer.

So, what does Metformin do? Well, that’s actually a very good question. It’s such a simple compound that it’s pretty much impossible to know all of its effects, but it’s best-known effect is to suppress hepatic gluconeogenesis, or the production of glucose in the liver, that gets released into the bloodstream. This is a boon for Type II diabetic patients in particular, and Metformin is a widely used anti-diabetic drug. In the United States, over 48 million prescriptions were filled in 2010 (source).

Recently, it has come under interest as a potential anti-cancer drug as a result of several studies carried out in the lab, but not in people.

The authors were curious if patients that had ovarian cancer and were also receiving metformin might fare better than those that were not on metformin. The authors identified 72 ovarian cancer patients who were diabetic and on metformin, 103 diabetic ovarian cancer patients not on metformin, and 178 ovarian cancer patients who were neither diabetic nor on metformin. The results were rather striking:

RESULTS: In a preliminary analysis of the OC cohort (72 cases and 143 controls), cases had better survival (5-year disease-specific survival for cases vs controls, 73% vs 44%; P . .0002). In the definitive analysis of the EOC cohort (61 cases and 178 controls), the distribution of age, disease stage, optimal cytoreduction, serous histology, and platinum chemotherapy remained similar between cases and controls (P > .05). Despite these similarities, cases had significantly better survival (5-year disease-specific survival for cases vs controls, 67% vs 47%; P . .007). On multivariate analysis, metformin remained an independent predictor of survival (hazard ratio, 2.2; 95% confidence interval, 1.2-3.8; P . .007) after controlling for disease stage, grade, histology, chemotherapy, body mass index, and surgical cytoreduction.

I would like to stress that five years after diagnosis, ovarian cancer patients that had been prescribed metformin were 30% more likely to still be alive.

The dose and duration of metformin used by these patients varied widely, and it is very possible that metformin might be even more effective than shown in this study if dosage and use is further refined. But, we must be careful: this is merely a case-control study. The golden standard is a controlled clinical trial with a placebo group. As it just so happens, there is a large scale clinical trial investigating metformin use in breast cancer (National Clinical Trial identifier NCT01101438). I will follow the results of this clinical trial with great interest!


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