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Patients with low risk, localized prostate cancer who are suitable for active surveillance do not benefit from daily use of metformin. In patients with high BMI, metformin is potentially detrimental, according to results from the MAST study.
Previously, it was suggested that metformin could be a useful adjuvant agent in cancer management, with the greatest benefits seen in colorectal and prostate cancer1. Biological, epidemiological, and clinical data support a rationale for the use of metformin in prostate cancer. However, much of the literature is focused on retrospective analyses, with metformin use being associated with type 2 diabetes.
The MAST trial (NCT01864096) is the first, prospective, and randomized study to explore the effect of daily use of metformin on the progression of low risk, localized prostate cancer. Dr. Antony Joshua, MBBS, PHD, of the Princes Margret Cancer Center, in Canada, presented the results2.
In the study, 407 men had a low risk prostate cancer diagnosis (Gleason score ≤6, ≤1/3 positive biopsy cores, <50% of any one core positive, clinical stage T1c-T2a, PSA ≤10 ng/ml) were 1:1 randomly assigned to active surveillance plus metformin or active surveillance plus placebo. Patients with a type 1 or type 2 diabetes diagnosis were excluded. Primary endpoints were time to pathological progression and time to definitive therapy. Biopsies were taken at baseline and at 18 and 36 months of follow up.
Metformin did not delay pathological progression versus placebo (HR 1.08; 95% CI 0.78-1.50; P=0.64) but did increase therapeutic progression (HR 1.75; 95% CI 0.99-3.03; P= 0.05). Exploratory subgroup analysis showed significantly increased pathological progression in patients with a BMI under or equal to 30 at study entry (n=105) treated with metformin versus placebo (HR 2.39; 93% CI 1.20-4.75; P=0.01). In addition, in patients with Gleason under or equal to 8 (n=11) a trend was observed for increased progression on metformin.
Based on these results, Dr. Joshua concluded: “Metformin does not prevent progression of low risk, localized prostate cancer suitable for active surveillance. In patients with a high BMI, metformin could even be detrimental. Therefore, further research is needed to understand the consequences of metformin on prostate cancer outcomes.”
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