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Metformin may act synergistically with androgen deprivation therapy to improve outcomes for men with advanced prostate cancer, according to findings of an observational study presented at the AUA annual meeting in Boston.
Boston-Metformin may act synergistically with androgen deprivation therapy (ADT) to improve outcomes for men with advanced prostate cancer, according to findings of an observational study presented at the AUA annual meeting in Boston.
The investigation included 87,344 patients identified from national Veterans Affairs databases who were diagnosed with prostate cancer between 2000 and 2008, received ADT for >6 months, and were not on concurrent radiotherapy. The men were categorized into three groups defined as non-diabetics (61%), diabetics on metformin (17%), and diabetics not on metformin (22%).
With follow-up data through May 2016, median overall survival for the non-diabetics, diabetics on metformin, and diabetics not on metformin was 7.1, 9.1, and 7.4 years, respectively. A multivariable Cox proportional hazards analysis controlling for age, comorbidity, year of diagnosis, PSA, and Gleason score showed that both overall survival and cancer-specific survival were significantly prolonged among the diabetics on metformin compared with the non-diabetic controls (hazard ratio=0.79 and 0.72, respectively; p<.01 for both endpoints).
Cancer-specific survival was also significantly improved in the men with diabetes not on metformin compared with the referent group (hazard ratio=0.91; p=.026), but overall survival was not significantly different (hazard ratio=0.99). The risk of skeletal-related events, which was evaluated as a marker of disease progression, was not significantly different in either of the diabetic groups compared with the controls.
“Previous studies have investigated the effects of metformin treatment in men with prostate cancer, but to our knowledge, ours is one of the largest studies of prostate cancer patients to date and also uniquely evaluates the subset of men on ADT,” said Kyle A. Richards, MD, assistant professor of urology at the University of Wisconsin, Madison.
“We were interested in studying this patient population because residual cancer cells after ADT demonstrate metabolic susceptibilities that make them amenable to synergistic treatment. Our finding of improved survival among the metformin-treated patients suggests that a prospective clinical trial is warranted.”
Next: Prospective clinical trial planned
Planning for a prospective clinical trial is in an early stage. In addition, in their research laboratory at the University of Wisconsin, David Jarrard, MD, and colleagues are trying to determine the mechanism(s) by which metformin may improve survival of prostate cancer patients on ADT.
“Basic science studies indicate that metformin has direct antineoplastic activity that may be mediated by mTOR inhibition, but its anticancer benefit may also be related to its effects on insulin and glucose,” Dr. Richards said.
“We are now analyzing data on metformin dose as well as HbA1c and blood glucose levels to try to better understand the mechanism for the benefit of metformin that we observed.”
Dr. Richards noted that the study has limitations related to its retrospective design. In particular, due to missing data in the VA database, it could not control for all prostate cancer-related prognostic variables.
The work is funded by DOD PCRP #150221. The contents do not represent the views of the U.S. Department of Veterans Affairs or the U.S. government.
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