Metformin aids in the stabilization of metastatic prostate cancer
Tuesday, May 6, 2014. An article published this year in European Urology reports the outcome of a Swiss trial involving men with castration-resistant prostate cancer (defined as a testosterone level of less than 50 ng/dL with progressive disease) who were given the antidiabetic drug metformin.
"Metformin has antiproliferative effects in preclinical models of prostate cancer via reduction of systemic insulin levels and inhibition of mammalian target of rapamycin (mTOR)," write authors Christian Rothermundt and his colleagues in their introduction. "In a recent population-based evaluation among 3837 diabetic patients with prostate cancer, metformin use was associated with reduced prostate cancer-specific mortality and reduced all-cause mortality."
For the trial, 44 nondiabetic men who had not been treated with chemotherapy for progressive, metastatic prostate cancer causing few or no symptoms were given 1000 milligrams metformin two times per day until disease progression. Assessment of disease status, including computed tomography of the abdomen, pelvis and chest; bone scanning, and serum prostate cancer specific antigen (PSA) level measurement was conducted every twelve weeks.
At twelve weeks, 36% of the group was progression-free, and 9% were still progression-free at 24 weeks. PSA doubling time, a measure of disease progression, was prolonged in more than half of the participants after starting metformin. The drug was also associated with improved insulin sensitivity.
"To our knowledge, this is the first prospective clinical trial reporting on treatment with the biguanide metformin in patients with progressive castration-resistant prostate cancer," the authors announce. "Testing metformin in an earlier prostate cancer disease setting and in combinations is of great interest, especially considering the additional effect of metformin on metabolic parameters," they conclude.
The journal Cancer Epidemiology, Biomarkers & Prevention published an article on June 10, 2013 which reports a benefit for the antidiabetic drug metformin in colorectal cancer survival.
The study involved 3,816 men and women with stage I-III colorectal cancer diagnosed between 2001 and 2006, including 207 diabetics who had been prescribed metformin, 108 diabetics who did not use the drug and 3,501 nondiabetics. The subjects were followed through 2010, during which 196 deaths occurred among those with diabetes and 1,897 occurred among the nondiabetics. Among the diabetic patients, 93 deaths were due to colorectal cancer, and 1,082 nondiabetic deaths were attributable to the disease.
When subjects treated with metformin were compared to diabetics who did not use the drug, a reduction in the risk of death due to colorectal cancer that "approached significance" was observed. However, those whose use of metformin was categorized as high intensity (higher dose), had a 56% lower risk of dying of the disease than diabetics who did not use the drug. Metformin use was additionally associated with a 31% lower adjusted risk of dying from any cause among diabetic subjects over follow-up.
"This study is the first, to the authors' knowledge, to assess the presence of an exposure response effect between increasing metformin use and colorectal cancer outcomes," authors Susan C. Spillane and her colleagues at St James Hospital in Dublin announce. "Significant associations were observed in stratified analyses of high intensity exclusive metformin usage and the results also suggest that metformin exposure may potentially improve survival relative to non-diabetic patients. Additional studies in larger population-based cohorts are required to further explore the influence of varying exposure levels and timing and to determine if any patient subgroups are more likely to benefit from metformin."
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