Increased tumor response to neoadjuvant therapy among rectal cancer patients taking angiotensin-converting enzyme inhibitors or angiotensin receptor blockers.
Increased tumor response to neoadjuvant therapy among rectal cancer patients taking angiotensin-converting enzyme inhibitors or angiotensin receptor blockers.
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DOI：
10.1002/cncr.30079
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发表时间：
2016-08-15
期刊：
影响因子：
6.2
通讯作者：
Ritter MA
中科院分区：
文献类型：
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作者：
Morris ZS;Saha S;Magnuson WJ;Morris BA;Borkenhagen JF;Ching A;Hirose G;McMurry V;Francis DM;Harari PM;Chappell R;Tsuji S;Ritter MA
血管紧张素转换酶抑制剂（ACEIs）和血管紧张素受体阻滞剂（ARBs）是常用的抗高血压药物，有报道称它们会影响异常的血管生成和失调的炎症反应。由于这些机制，我们假设这些药物可能会影响直肠癌患者对新辅助放疗的肿瘤反应。1999年至2012年间，在威斯康星大学（UW）接受新辅助放射治疗的115名患者被确定。采用匿名患者数据进行单因素分析。在第二个独立的数据集中，在1995年至2010年期间，在夏威夷大学皇后医学中心（UH）接受新辅助放射治疗的186名直肠癌患者被确定。这些数据和以前一样被独立分析。对汇总数据进行多变量分析。在UW数据集中服用ACEIs/ arb的患者中，观察到新辅助治疗的病理完全缓解（pCR）率显著增加3倍（52% vs 17%, P = 0.001）。这一发现在UH数据集中得到了证实，其中观察到pCR率显著增加了2倍（24%对12%，P = 0.03）。在服用和未服用acei / arb的患者之间，确定的患者和治疗特征是平衡的。其他药物（包括他汀类药物、二甲双胍和阿司匹林）对pCR率没有显著影响。综合数据的多变量分析表明，ACEI/ARB的使用是pCR的强预测因子（优势比4.02；95%可信区间2.06-7.82;P < 0.001）。在直肠癌患者中偶然使用ACEIs/ arb与新辅助治疗后pCR率显著增加相关。
Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are commonly used antihypertensive medications that have been reported to affect aberrant angiogenesis and the dysregulated inflammatory response. Because of such mechanisms, it was hypothesized that these medications might affect the tumor response to neoadjuvant radiation in patients with rectal cancer. One hundred fifteen patients who were treated with neoadjuvant radiation at the University of Wisconsin (UW) between 1999 and 2012 were identified. Univariate analyses were performed with anonymized patient data. In a second independent data set, 186 patients with rectal cancer who were treated with neoadjuvant radiation at the Queen’s Medical Center of the University of Hawaii (UH) between 1995 and 2010 were identified. These data were independently analyzed as before. Multivariate analyses were performed with aggregate data. Among patients taking ACEIs/ARBs in the UW data set, a significant 3-fold increase in the rate of pathologic complete response (pCR) to neoadjuvant therapy (52% vs 17%, P = .001) was observed. This finding was confirmed in the UH data set, in which a significant 2-fold–increased pCR rate (24% vs 12%, P = .03) was observed. Identified patient and treatment characteristics were otherwise balanced between patients taking and not taking ACEIs/ARBs. No significant effect was observed on pCR rates with other medications, including statins, metformin, and aspirin. Multivariate analyses of aggregate data identified ACEI/ARB use as a strong predictor of pCR (odds ratio, 4.02; 95% confidence interval, 2.06–7.82; P < .001). The incidental use of ACEIs/ARBs among patients with rectal cancer is associated with a significantly increased rate of pCR after neoadjuvant treatment.