Metformin Use is Associated with Improved Survival for Patients with Advanced Prostate Cancer on Androgen Deprivation Therapy.

Abstract

PURPOSE:

Metformin is commonly prescribed for patients with type 2 diabetes mellitus. We hypothesized that metformin plus androgen deprivation therapy may be beneficial in combination. Our objective was to assess this combination in a retrospective cohort of patients with advanced prostate cancer.

MATERIALS AND METHODS:

Using national Veterans Affairs databases we identified all men diagnosed with prostate cancer between 2000 and 2008 who were treated with androgen deprivation therapy with followup through May 2016. Study exclusions included treatment with androgen deprivation therapy for 6 months or longer, or receipt of androgen deprivation therapy concurrently with localized radiation. Three patient cohorts were developed, including no diabetes mellitus, diabetes mellitus with no metformin and diabetes mellitus with metformin. Cox proportional HRs were calculated for overall survival, skeletal related events and cancer specific survival.

RESULTS:

After exclusions the cohort consisted of 87,344 patients, including 61% with no diabetes mellitus, 22% with diabetes mellitus and no metformin, and 17% with diabetes mellitus on metformin. Cox proportional hazard analysis of overall survival showed improved survival in men with diabetes mellitus on metformin (HR 0.82, 95% CI 0.78-0.86) compared to those with diabetes mellitus who were not on metformin (HR 1.03, 95% CI 0.99-1.08). The reference group was men with no diabetes mellitus. Cox proportional hazard analysis of predictors of skeletal related events revealed a HR of 0.82 (95% CI 0.72-0.93) in men with diabetes mellitus on metformin. Cox proportional hazard analysis of cancer specific survival showed improved survival in men with diabetes mellitus on metformin (HR 0.70, 95% CI 0.64-0.77) vs those with diabetes mellitus without metformin (HR 0.93, 95% CI 0.85- 1.00). The reference group was men with no diabetes mellitus.

CONCLUSIONS:

Metformin use in veterans with prostate cancer who receive androgen deprivation therapy is associated with improved oncologic outcomes. This association should be evaluated in a prospective clinical trial.

• Authors: Kyle A Richards, Jinn-Ing Liou, Vincent L Cryns, Tracy M Downs, E Jason Abel, David F Jarrard
• Journal: The Journal of urology (J Urol) Vol. 200 Issue 6 Pg. 1256-1263 (12 2018) ISSN: 1527-3792 [Electronic] United States
• PMID: 29940252 (Publication Type: Journal Article)
• Copyright: Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Chemical References

• Androgen Antagonists
• Hypoglycemic Agents
• Metformin

Topics

• Aged
• Androgen Antagonists (therapeutic use)
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Cancer Survivors (statistics & numerical data)
• Databases, Factual (statistics & numerical data)
• Diabetes Mellitus, Type 2 (drug therapy, mortality)
• Humans
• Hypoglycemic Agents (therapeutic use)
• Male
• Metformin (therapeutic use)
• Neoplasm Staging
• Prospective Studies
• Prostatic Neoplasms (drug therapy, mortality, pathology)
• Retrospective Studies
• Survival Analysis
• Treatment Outcome
• United States (epidemiology)
• United States Department of Veterans Affairs
• Veterans (statistics & numerical data)