The effect of metformin on cancer-specific survival outcomes in diabetic patients undergoing radical cystectomy for urothelial carcinoma of the bladder
The effect of metformin on cancer-specific survival outcomes in diabetic patients undergoing radical cystectomy for urothelial carcinoma of the bladder
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DOI：
10.1016/j.urolonc.2015.05.024
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发表时间：
2015-09-01
影响因子：
2.7
通讯作者：
Kulkarnia, Girish S.
中科院分区：
文献类型：
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作者：
Nayan, Madhur;Bhindi, Bimal;Kulkarnia, Girish S.
目的：二甲双胍是糖尿病的一线口服治疗药物，具有抗癌特性。我们的目的是评估二甲双胍的使用和糖尿病患者接受根治性cytotony（RC）治疗膀胱癌（BC）的肿瘤学结局之间的关联。方法：一个单一的机构回顾性队列（1997年1月至2013年6月）的糖尿病患者接受RC组装。在手术时评估药物使用情况。结果指标为无复发生存期（RFS）。BC特异性生存期（BCSS）和总生存期（OS）。采用多变量考克斯比例风险模型。要创建简约的模型，估计方法（10%阈值）的变化被用来作为最终模型的变量选择策略，分别为每个结果measure.Results：421例患者中，85（20%）有糖尿病。39例（46%）患者接受二甲双胍治疗。在糖尿病患者中，有21例BC复发，16例死于BC，30例死亡。在单变量分析中，糖尿病患者使用二甲双胍与RFS改善相关（风险比= 0. 54，95% CI：0. 33（1. 88，P = 0. 013）），并有改善BCSS的趋势（风险比= 0. 65，95% CI：0. 40 - 1. 07，P = 1. 087），但与OS无关（P = 0. 87）。在多变量模型中，糖尿病患者使用二甲双胍与RFS（校正风险比= 0.38，95% CI：0.20-0.72，P = 0.003）和BCSS（校正风险比= 0.57，95% CI：0.35-0.91，P = 0.019）显著改善相关，但与OS无关（P = 0.89）。其他口服降糖药或胰岛素的使用与肿瘤学outcomes.Conclusions：我们的研究是第一个报告二甲双胍的使用和改善RFS和BCSS的糖尿病患者接受RC之间的关联。鉴于其低成本和非糖尿病患者的安全性，需要进一步研究来评估二甲双胍在BC中的潜在治疗和预防作用。(C)2015 Elsevier Inc. All rights reserved.
Purpose: Metformin, a first-line oral therapy for diabetes, has anticancer properties. Our objective was to evaluate the association between metformin use and oncologic outcomes in diabetic patients undergoing radical cystectotny (RC) for bladder cancer (BC).Methods: A single-institution retrospective cohort (January 1997 June 2013) of diabetic patients undergoing RC was assembled. Medication use was assessed at time of surgery. Outcome measures were recurrence-free survival (RFS). BC-specific survival (BCSS), and overall survival (OS). Multivariable Cox proportional hazards models were used. To create parsimonious models, the change of estimate approach (10% threshold) was used as a variable selection strategy for final model inclusion separately for each outcome measure.Results: Of 421 patients, 85 (20%) had diabetes. There were 39 (46%) patients on metformin therapy. Among diabetic patients, there were 21 patients with BC recurrence, 16 who died of BC, and 30 who died overall. In univariate analyses, metformin use among diabetic patients was associated with improved RFS (hazard ratio = 0.54, 95% Cl: 0.33 (1.88, P = 0.013) and trended toward improved BCSS (hazard ratio = 0.65, 95% Cl: 0.40-1.07, P = 1.087), but not with OS (P = 0.87). In multivariable models, metformin use among diabetic patients was associated with significantly improved RFS (adjusted hazard ratio = 0.38, 95% CI: 0.20-0.72, P = 0.003) and BCSS (adjusted hazard ratio = 0.57, 95% Cl: 0.35-0.91, P = 0.019), but not with OS (P = 0.89). Use of other oral hypoglycemic agents or insulin was not associated with oncologic outcomes.Conclusions: Our study is among the first to report an association between metformin use and improved RFS and BCSS in diabetic patients undergoing RC. Given its low cost and demonstrated safety among nondiabetic patients, further studies are warranted to evaluate potential therapeutic and preventive roles of metformin in BC. (C) 2015 Elsevier Inc. All rights reserved.