舒林酸和厄洛替尼与安慰剂治疗家族性腺瘤性息肉病结直肠肿瘤的比较：一项随机临床试验的二次分析。
Association of Sulindac and Erlotinib vs Placebo With Colorectal Neoplasia in Familial Adenomatous Polyposis: Secondary Analysis of a Randomized Clinical Trial.
机构信息
Huntsman Cancer Institute, The University of Utah, Salt Lake City.
Department of Medicine (Gastroenterology), The University of Utah, Salt Lake City.
出版信息
JAMA Oncol. 2018 May 1;4(5):671-677. doi: 10.1001/jamaoncol.2017.5431.
IMPORTANCE
Patients with familial adenomatous polyposis (FAP) are at markedly increased risk for colorectal polyps and cancer. A combination of sulindac and erlotinib led to a 71% reduction in duodenal polyp burden in a phase 2 trial.
OBJECTIVE
To evaluate effect of sulindac and erlotinib on colorectal adenoma regression in patients with FAP.
DESIGN, SETTING, AND PARTICIPANTS: Prespecified secondary analysis for colorectal adenoma regression was carried out using data from a double-blind, randomized, placebo-controlled trial, enrolling 92 patients with FAP, conducted from July 2010 to June 2014 in Salt Lake City, Utah.
INTERVENTIONS
Patients were randomized to sulindac, 150 mg twice daily, and erlotinib, 75 mg daily (n = 46), vs placebo (n = 46) for 6 months.
MAIN OUTCOMES AND MEASUREMENTS
The total number of polyps in the intact colorectum, ileal pouch anal anastomosis, or ileo-rectum were recorded at baseline and 6 months. The primary outcomes were change in total colorectal polyp count and percentage change in colorectal polyps, following 6 months of treatment.
RESULTS
Eighty-two randomized patients (mean [SD] age, 40 [13] years; 49 [60%] women) had colorectal polyp count data available for this secondary analysis: 22 with intact colon, 44 with ileal pouch anal anastomosis and 16 with ileo-rectal anastomosis; 41 patients received sulindac/erlotinib and 41 placebo. The total colorectal polyp count was significantly different between the placebo and sulindac-erlotinib group at 6 months in patients with net percentage change of 69.4% in those with an intact colorectum compared with placebo (95% CI, 28.8%-109.2%; P = .009).
CONCLUSION AND RELEVANCE
In this double-blind, placebo-controlled, randomized trial we showed that combination treatment with sulindac and erlotinib compared with placebo resulted in significantly lower colorectal polyp burden after 6 months of treatment. There was a reduction in polyp burden in both those with an entire colorectum and those with only a rectal pouch or rectum.
TRIAL REGISTRATION
clinicaltrials.gov Identifier: NCT01187901.
重要性
家族性腺瘤性息肉病（FAP）患者结直肠息肉和癌症的风险明显增加。在一项 2 期试验中，联合应用舒林酸和厄洛替尼可使十二指肠息肉负担减少 71%。
目的
评估舒林酸和厄洛替尼对 FAP 患者结直肠腺瘤消退的影响。
设计、地点和参与者：这是一项双盲、随机、安慰剂对照试验的预设次要分析，纳入了 2010 年 7 月至 2014 年 6 月在美国犹他州盐湖城进行的 92 例 FAP 患者，这些患者接受舒林酸，每日 2 次，每次 150mg，厄洛替尼，每日 75mg（n=46）或安慰剂（n=46）治疗 6 个月。
干预措施
患者随机分为舒林酸，每日 2 次，每次 150mg，厄洛替尼，每日 75mg（n=46），或安慰剂（n=46）治疗 6 个月。
主要结局和测量指标
基线和 6 个月时记录完整结直肠、回肠袋肛门吻合术或回直肠中的息肉总数。主要结局是 6 个月治疗后结直肠总息肉计数的变化和结直肠息肉的百分比变化。
结果
82 名随机患者（平均[SD]年龄，40[13]岁；49[60%]女性）可提供结直肠息肉计数数据进行二次分析：22 例有完整结肠，44 例有回肠袋肛门吻合术，16 例有回直肠吻合术；41 例接受舒林酸/厄洛替尼治疗，41 例接受安慰剂治疗。与安慰剂组相比，完整结直肠中净百分比变化为 69.4%的患者，舒林酸/厄洛替尼组 6 个月时总结直肠息肉计数有显著差异（95%CI，28.8%-109.2%；P=0.009）。
结论和相关性
在这项双盲、安慰剂对照、随机试验中，我们发现与安慰剂相比，舒林酸和厄洛替尼联合治疗 6 个月后结直肠息肉负担明显降低。在整个结直肠和仅直肠袋或直肠患者中均有息肉负担减少。
试验注册
clinicaltrials.gov 标识符：NCT01187901。
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