Targeting Tumor Metabolism With Statins During Treatment for Advanced-stage Pancreatic Cancer.
Targeting Tumor Metabolism With Statins During Treatment for Advanced-stage Pancreatic Cancer.
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DOI：
10.1097/coc.0000000000000433
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发表时间：
2018-11
期刊：
影响因子：
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通讯作者：
Champ CE
中科院分区：
文献类型：
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作者：
Iarrobino NA;Gill B;Bernard ME;Mishra MV;Champ CE
越来越多的临床前数据表明，他汀类药物可能具有有效的抗肿瘤作用，但这些药物与标准疗法的相互作用以及在该人群中的临床结果尚不清楚。我们评估了他汀类药物对接受各种治疗的晚期胰腺腺癌患者预后的影响。在IRB批准后，我们进行了一项由303名新诊断的晚期胰腺腺癌患者组成的回顾性队列研究，以确定他汀类药物使用对预后的影响。采用单变量和多变量Cox比例风险回归模型估计风险比。使用Kaplan-Meier生存分析来估计总生存期、远处转移和局部失败的时间。评估基线和有效的他汀类药物使用情况，并进行亚分析，排除随访时间低于6个月的患者，以减轻不朽时间偏差的风险。在该队列中，既往（p=0.021）和有效（p=0.030）他汀类药物的使用与生存率的提高相关。手术、放化疗和他汀类药物的使用提高了2年生存率（84.1% vs. 55.0%, p<0.001）。在多变量分析中，他汀类药物暴露与总生存率相关（HR 0.662, p=0.027），与远处转移自由相关（HR 0.577, p=0.060）。合并症与结果无显著相关性。他汀类药物的使用与晚期胰腺腺癌患者总生存率的提高相关。这一数据支持了先前在早期胰腺腺癌和其他癌症部位的发现。据我们所知，这是第一份研究他汀类药物作为晚期胰腺腺癌患者补充治疗选择的疗效的报告。
A growing body of preclinical data suggests that statins may exert potent anti-tumor effects, yet the interactions of these medications with standard therapies and clinical outcomes in this population is less clear. We assessed the impact of statin use on outcomes in patients with advanced-stage pancreatic adenocarcinoma undergoing various treatments. After IRB approval, we conducted a retrospective-cohort study consisting of 303 newly diagnosed advanced-stage pancreatic adenocarcinoma patients to determine the impact of statin use on outcomes. Univariate and multivariable Cox proportional hazard regression models were utilized to estimate hazard ratios. Time-to-event was estimated using Kaplan-Meier survival analysis for overall survival, distant metastasis, and locoregional failure. Baseline and active statin usage were assessed and to mitigate risk of immortal time bias, sub-analysis excluding patients with under 6 months of follow-up was conducted. Both prior (p=0.021) and active (p=0.030) statin usage correlated with improved survival in this cohort. Surgery, chemoradiation, and statin use improved 2-year survival rates (84.1 vs. 55.0%, p<0.001). On multivariable analysis, statin exposure was associated with overall survival (HR 0.662, p=0.027) and trended to significance for freedom from distant metastasis (HR 0.577, p=0.060). Comorbid conditions were not significantly associated with outcomes. Statin use was associated with improved overall survival in advanced-stage pancreatic adenocarcinoma patients. This data supports previous findings in early-stage pancreatic adenocarcinoma and other cancer sites. To our knowledge this is the first report to examine the efficacy of statin use as a supplementary treatment option in advanced-stage pancreatic adenocarcinoma patients.