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.
Written by:
Spratt DE, Zhang C, Zumsteg ZS, Pei X, Zhang Z, Zelefsky MJ. Are you the author?
Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY USA.
Reference: Eur Urol. 2012 Dec 14. pii: S0302-2838(12)01472-8.
doi: 10.1016/j.eururo.2012.12.004
PubMed Abstract
PMID: 23287698
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