Nayan Madhur, Macdonald Erin M, Juurlink David N, Austin Peter C, Finelli Antonio, Kulkarni Girish S, Hamilton Robert J
Division of Urology, Departments of Surgery and Surgical Oncology, Princess Margaret Cancer Centre, University Health Network and the University of Toronto, Toronto, Canada.
Institute for Clinical Evaluative Sciences, Toronto, Canada.
Pharmacol Res. 2016 Nov;113(Pt A):468-474. doi: 10.1016/j.phrs.2016.09.027. Epub 2016 Sep 24.
Survival rates in kidney cancer have improved little over time, and diabetes may be an independent risk factor for poor survival in kidney cancer. We sought to determine whether medications with putative anti-neoplastic properties (statins, metformin and non-steroidal anti-inflammatory drugs (NSAIDs)) are associated with survival in diabetics with kidney cancer. We conducted a population-based cohort study utilizing linked healthcare databases in Ontario, Canada. Patients were aged 66 or older with newly diagnosed diabetes and a subsequent diagnosis of incident kidney cancer. Receipt of metformin, statins or NSAIDs was defined using prescription claims. The primary outcome was all-cause mortality and the secondary outcome was cancer-specific mortality. We used multivariable Cox proportional hazard regression, with medication use modeled with time-varying and cumulative exposure analyses to account for intermittent use. During the 14-year study period, we studied 613 patients. Current statin use was associated with a markedly reduced risk of death from any cause (adjusted hazard ratio 0.74; 95% CI 0.59-0.91) and death due to kidney cancer (adjusted hazard ratio 0.71; 95% CI 0.51-0.97). However, survival was not associated with current use of metformin or NSAIDs, or cumulative exposure to any of the medications studied. Among diabetic patients with kidney cancer, survival outcomes are associated with active statin use, rather than total cumulative use. These findings support the use of randomized trials to confirm whether diabetics with kidney cancer should be started on a statin at the time of cancer diagnosis to improve survival outcomes.
随着时间的推移,肾癌的生存率几乎没有提高,糖尿病可能是肾癌患者生存率低的一个独立危险因素。我们试图确定具有假定抗肿瘤特性的药物(他汀类药物、二甲双胍和非甾体抗炎药(NSAIDs))是否与糖尿病肾癌患者的生存率相关。我们利用加拿大安大略省的关联医疗数据库进行了一项基于人群的队列研究。患者年龄在66岁及以上,新诊断为糖尿病,随后被诊断为新发肾癌。通过处方记录确定是否使用二甲双胍、他汀类药物或NSAIDs。主要结局是全因死亡率,次要结局是癌症特异性死亡率。我们使用多变量Cox比例风险回归,将药物使用情况建模为随时间变化和累积暴露分析,以考虑间歇性使用。在14年的研究期间,我们研究了613名患者。目前使用他汀类药物与任何原因导致的死亡风险显著降低(调整后的风险比为0.74;95%可信区间为0.59-0.91)以及肾癌导致的死亡风险降低(调整后的风险比为0.71;95%可信区间为0.51-0.97)相关。然而,生存率与目前使用二甲双胍或NSAIDs以及所研究的任何药物的累积暴露无关。在糖尿病肾癌患者中,生存结局与积极使用他汀类药物有关,而不是与总累积使用量有关。这些发现支持使用随机试验来确认糖尿病肾癌患者在癌症诊断时是否应开始使用他汀类药物以改善生存结局。