Efficacy of Difluoromethylornithine and Aspirin for Treatment of Adenomas and Aberrant Crypt Foci in Patients with Prior Advanced Colorectal Neoplasms.
Efficacy of Difluoromethylornithine and Aspirin for Treatment of Adenomas and Aberrant Crypt Foci in Patients with Prior Advanced Colorectal Neoplasms.
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二氟甲基鸟氨酸和阿司匹林治疗既往晚期结直肠肿瘤患者的腺瘤和异常隐窝病灶的疗效。
DOI：
10.1158/1940-6207.capr-19-0167
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发表时间：
2019
期刊：
影响因子：
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通讯作者：
Sweetser,SethR
中科院分区：
文献类型：
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作者：
Sinicrope,FrankA;Velamala,PruthviR;Song,LouisMWongKee;Viggiano,ThomasR;Bruining,DavidH;Rajan,Elizabeth;Gostout,ChristopherJ;Kraichely,RobertE;Buttar,NavtejS;Schroeder,KennethW;Kisiel,JohnB;Larson,MarkV;Sweetser,SethR
二氟甲基鸟氨酸（DFMO），一种多胺合成抑制剂，被证明与非甾体抗炎药协同作用，用于化学预防结直肠肿瘤。我们确定了DFMO联合阿司匹林在既往患有晚期腺瘤或癌症的患者中预防结直肠腺瘤和直肠异常隐窝灶（ACF）消退的有效性和安全性。一项双盲、安慰剂对照试验在104名受试者（46-83岁）中进行，随机（1:1）接受每日DFMO（口服500毫克）加阿司匹林（325毫克）或匹配的安慰剂，为期一年。所有息肉均在基线时切除。在一年的结肠镜检查中评估腺瘤数目（主要终点）和直肠ACF（指数簇和总）。彩色内窥镜检查ACF。毒性监测，包括听力测定。87名受试者可评估腺瘤或ACF调节（n= 62）。在治疗一年时，DFMO加阿司匹林组（n= 42）中有16名（38.1%）受试者检测到腺瘤，而安慰剂组（n= 44， P= 0.790）中有18名（40.9%）受试者检测到腺瘤；晚期腺瘤相似（n= 3/组）。与安慰剂相比，DFMO加阿司匹林与直肠ACF中位数降低有统计学意义（P= 0.036）。治疗组与安慰剂组相比，直肠ACF总负荷也较基线降低（74%对45%，P= 0.020）。与安慰剂组相比，治疗组未观察到包括耳毒性在内的不良事件增加。虽然一年内DFMO加阿司匹林不能显著减少腺瘤复发，但联合用药可显著减少直肠ACF数，这与化学预防作用一致。
Difluoromethylornithine (DFMO), an inhibitor of polyamine synthesis, was shown to act synergistically with a NSAID for chemoprevention of colorectal neoplasia. We determined the efficacy and safety of DFMO plus aspirin for prevention of colorectal adenomas and regression of rectal aberrant crypt foci (ACF) in patients with prior advanced adenomas or cancer. A double-blinded, placebo-controlled trial was performed in 104 subjects (age 46–83) randomized (1:1) to receive daily DFMO (500 mg orally) plus aspirin (325 mg) or matched placebos for one year. All polyps were removed at baseline. Adenoma number (primary endpoint) and rectal ACF (index cluster and total) were evaluated at a one year colonoscopy. ACF were identified by chromoendoscopy. Toxicity was monitored, including audiometry. Eighty-seven subjects were evaluable for adenomas or ACF modulation (n= 62). At one year of treatment, adenomas were detected in 16 (38.1%) subjects in the DFMO plus aspirin arm (n= 42) versus 18 (40.9%) in the placebo arm (n= 44;P= 0.790); advanced adenomas were similar (n= 3/arm). DFMO plus aspirin was associated with a statistically significant reduction in the median number of rectal ACF compared with placebo (P= 0.036). Total rectal ACF burden was also reduced in the treatment versus the placebo arm relative to baseline (74% vs. 45%,P= 0.020). No increase in adverse events, including ototoxicity, was observed in the treatment versus placebo arms. While adenoma recurrence was not significantly reduced by one year of DFMO plus aspirin, the drug combination significantly reduced rectal ACF number consistent with a chemopreventive effect.