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April 19, 2013
Patients on Metformin Had the Lowest Prostate-Cancer Specific Mortality
Eur Urol 2012 Dec 14;63(4)709-716, DE Spratt, C Zhang, ZS Zumsteg, et al
Among 2900 localized prostate cancer patients receiving radiation therapy, the authors studied retrospectively the impact of metformin on disease progression. Compared to diabetic non-metformin users (22%) and non-diabetic controls (8%), patients on metformin had the lowest prostate-cancer specific mortality (3%), which was statistically significant. Metformin users also had a lower incidence of biochemical failure and distant metastasis.
Background: In vitro data and early clinical results suggest that metformin has desirable antineoplastic effects and has a theoretical benefit on castration-resistant prostate cancer (CRPC).
Objective: To determine whether the use of metformin would be associated with improved clinical outcomes and a reduction in the development of CRPC.
Design, Setting, and Participants: Data from 2901 consecutive patients (157 metformin, 162 diabetic non-metformin, and 2582 nondiabetic) with localized prostate cancer treated with external-beam radiation therapy from 1992 to 2008 were collected from a single institution in the United States.
Intervention: Use of metformin in localized prostate cancer.
Outcome Measurements and Statistical Analysis: Univariate and multivariate regression models utilizing k-sample, Fine and Gray, Cox regression, log-rank, and Kaplan-Meier methods to assess prostate-specific antigen-recurrence-free survival (PSA-RFS), distant metastases-free survival (DMFS), prostate cancer-specific mortality (PCSM), overall survival (OS), and development of CRPC.
Results and Limitations: With a median follow-up of 8.7 yr, the 10-yr actuarial rates for metformin, diabetic non-metformin, and nondiabetic patients for PCSM were 2.7%, 21.9%, and 8.2% (log-rank p ≤ 0.001), respectively. Metformin use independently predicted (correcting for PSA, T stage, Gleason score, age, diabetic status, and androgen-deprivation therapy use) improvement in all outcomes compared with the diabetic non-metformin group; PSA-RFS (hazard ratio [HR]: 1.99 [1.24–3.18]; p = 0.004), DMFS (adjusted HR: 3.68 [1.78–7.62]; p < 0.001), and PCSM (HR: 5.15 [1.53–17.35]; p = 0.008). Metformin use was also independently associated with a decrease in the development of CRPC in patients experiencing biochemical failure compared with diabetic non-metformin patients (odds ratio: 14.81 [1.83–119.89]; p = 0.01). The retrospective study design was the primary limitation of the study.
Conclusions: To our knowledge, our results are the first clinical data to indicate that metformin use may improve PSA-RFS, DMFS, PCSM, OS, and reduce the development of CRPC in prostate cancer patients. Further validation of metformin's potential benefits is warranted.
Post Edited (Jerry L.) : 4/26/2013 6:48:04 PM (GMT-6)