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在晚期胰腺癌治疗期间用他汀类药物靶向肿瘤代谢

Targeting Tumor Metabolism With Statins During Treatment for Advanced-stage Pancreatic Cancer.

作者信息

Iarrobino Nick A, Gill Beant, Bernard Mark E, Mishra Mark V, Champ Colin E

机构信息

*University of Pittsburgh School of Medicine †Department of Radiation Oncology, University of Pittsburgh Medical Center, Pittsburgh, PA ‡Department of Radiation Medicine, University of Kentucky, Lexington, KY §Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD.

出版信息

Am J Clin Oncol. 2018 Nov;41(11):1125-1131. doi: 10.1097/COC.0000000000000433.

Abstract

INTRODUCTION

A growing body of preclinical data suggests that statins may exert potent antitumor 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.

MATERIALS AND METHODS

After institutional review board 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 (HRs). 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, subanalysis excluding patients with under 6 months of follow-up was conducted.

RESULTS

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.

CONCLUSIONS

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.

摘要

引言

越来越多的临床前数据表明,他汀类药物可能具有强大的抗肿瘤作用,但这些药物与该人群中标准疗法的相互作用以及临床结局尚不清楚。我们评估了使用他汀类药物对接受各种治疗的晚期胰腺腺癌患者结局的影响。

材料与方法

经机构审查委员会批准后,我们进行了一项回顾性队列研究,纳入303例新诊断的晚期胰腺腺癌患者,以确定使用他汀类药物对结局的影响。采用单变量和多变量Cox比例风险回归模型来估计风险比(HRs)。使用Kaplan-Meier生存分析来估计总生存、远处转移和局部区域复发的事件发生时间。评估了基线和当前他汀类药物的使用情况,为减轻不朽时间偏倚的风险,进行了排除随访时间不足6个月患者的亚分析。

结果

在该队列中,既往使用(P=0.021)和当前使用(P=0.030)他汀类药物均与生存改善相关。手术、放化疗和使用他汀类药物可提高2年生存率(84.1%对55.0%;P<0.001)。多变量分析显示,他汀类药物暴露与总生存相关(HR,0.662;P=0.027),且在无远处转移方面有显著趋势(HR,0.577;P=0.060)。合并症与结局无显著相关性。

结论

使用他汀类药物与晚期胰腺腺癌患者的总生存改善相关。该数据支持先前在早期胰腺腺癌和其他癌症部位的研究结果。据我们所知,这是首份研究他汀类药物作为晚期胰腺腺癌患者辅助治疗选择疗效的报告。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4417/6123314/c6de0f8ee896/nihms939570f1.jpg

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