依氟鸟氨酸联合舒林酸不能延缓家族性腺瘤性息肉病的疾病进展—小柯机器人—科学网

依氟鸟氨酸联合舒林酸不能延缓家族性腺瘤性息肉病的疾病进展 作者： 发布时间：2020/9/14 13:47:17 美国癌症预防制药公司Alfred Cohen团队研究了依氟鸟氨酸联合舒林酸延缓家族性腺瘤性息肉病患者疾病进展的效果。2020年9月10日，该研究发表在《新英格兰医学杂志》上。

与单用药物相比，依氟鸟氨酸联合舒林酸治疗家族性腺瘤性息肉病患者在延缓病情进展方面的有效性和安全性尚不清楚。

研究组招募了171例家族性腺瘤性息肉病成人患者，根据息肉负荷最高的解剖部位和手术状况对患者进行分层。将其按1：1：1随机分组，其中57例患者接受依氟鸟氨酸治疗，58例接受舒林酸治疗，56例接受依氟鸟氨酸与舒林酸联合治疗，为期48个月。主要终点为疾病进展，定义为大手术、内镜切除晚期腺瘤、确诊直肠或囊袋高度不典型增生、或十二指肠疾病进展的综合结局。

依氟鸟氨酸联合舒林酸组的疾病进展率为32%，舒林酸组为38%，依氟鸟氨酸组为40%，依氟鸟氨酸联合舒林酸组与舒林酸组相比，风险比为0.71，与依氟鸟氨酸组相比，风险比为0.66。在37例结肠切除术患者中，3组的疾病进展率分别为17％、46%和42%，依氟鸟氨酸联合舒林酸组与其他两组的风险比分别为0.30和0.20；在34例直肠或回肠袋息肉病患者中，3组的疾病进展率分别为36%、18%和42%，风险比分别为2.03和0.84；在100例十二指肠息肉病患者中，3组的疾病进展率分别为36％、41％和39％。各治疗组的不良事件和严重不良事件发生率相差不大。

研究结果表明，依氟鸟氨酸联合舒林酸治疗家族性腺瘤性息肉病，并不能显著降低疾病进展风险。

附：英文原文

Title: Eflornithine plus Sulindac for Prevention of Progression in Familial Adenomatous Polyposis

Author: Carol A. Burke, M.D.,, Evelien Dekker, M.D.,, Patrick Lynch, M.D.,, N. Jewel Samadder, M.D.,, Francesc Balaguer, M.D.,, Robert H neburg, M.D.,, John Burn, M.D.,, Antoni Castells, M.D.,, Steven Gallinger, M.D.,, Ramona Lim, M.D.,, Elena M. Stoffel, M.D.,, Samir Gupta, M.D.,, Alex Henderson, M.D.,, Frank G. Kallenberg, M.D.,, Priyanka Kanth, M.D.,, Victorine H. Roos, M.D.,, Gregory G. Ginsberg, M.D.,, Frank A. Sinicrope, M.D.,, Christian P. Strassburg, M.D.,, Eric Van Cutsem, M.D.,, James Church, M.D.,, Fiona Lalloo, M.D.,, Field F. Willingham, M.D., M.P.H.,, Paul E. Wise, M.D.,, William M. Grady, M.D.,, Molly Ford, M.D.,, Jennifer M. Weiss, M.D.,, Robert Gryfe, M.D.,, Anil K. Rustgi, M.D.,, Sapna Syngal, M.D.,, and Alfred Cohen, M.D.

Issue Volume: 2020-09-10

Abstract:

Background

The efficacy and safety of combination therapy with eflornithine and sulindac, as compared with either drug alone, in delaying disease progression in patients with familial adenomatous polyposis are unknown.

Methods

We evaluated the efficacy and safety of the combination of eflornithine and sulindac, as compared with either drug alone, in adults with familial adenomatous polyposis. The patients were stratified on the basis of anatomical site with the highest polyp burden and surgical status; the strata were precolectomy (shortest projected time to disease progression), rectal or ileal pouch polyposis after colectomy (longest projected time), and duodenal polyposis (intermediate projected time). The patients were then randomly assigned in a 1:1:1 ratio to receive 750 mg of eflornithine, 150 mg of sulindac, or both once daily for up to 48 months. The primary end point, assessed in a time-to-event analysis, was disease progression, defined as a composite of major surgery, endoscopic excision of advanced adenomas, diagnosis of high-grade dysplasia in the rectum or pouch, or progression of duodenal disease.

Results

A total of 171 patients underwent randomization. Disease progression occurred in 18 of 56 patients (32%) in the eflornithine sulindac group, 22 of 58 (38%) in the sulindac group, and 23 of 57 (40%) in the eflornithine group, with a hazard ratio of 0.71 (95% confidence interval [CI], 0.39 to 1.32) for eflornithine sulindac as compared with sulindac (P=0.29) and 0.66 (95% CI, 0.36 to 1.24) for eflornithine sulindac as compared with eflornithine. Among 37 precolectomy patients, the corresponding values in the treatment groups were 2 of 12 patients (17%), 6 of 13 (46%), and 5 of 12 (42%) (hazard ratios, 0.30 [95% CI, 0.07 to 1.32] and 0.20 [95% CI, 0.03 to 1.32]); among 34 patients with rectal or ileal pouch polyposis, the values were 4 of 11 patients (36%), 2 of 11 (18%), and 5 of 12 (42%) (hazard ratios, 2.03 [95% CI, 0.43 to 9.62] and 0.84 [95% CI, 0.24 to 2.90]); and among 100 patients with duodenal polyposis, the values were 12 of 33 patients (36%), 14 of 34 (41%), and 13 of 33 (39%) (hazard ratios, 0.73 [95% CI, 0.34 to 1.52] and 0.76 [95% CI, 0.35 to 1.64]). Adverse and serious adverse events were similar across the treatment groups.

Conclusions

In this trial involving patients with familial adenomatous polyposis, the incidence of disease progression was not significantly lower with the combination of eflornithine and sulindac than with either drug alone.

DOI: 10.1056/NEJMoa1916063

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期刊信息

The New England Journal of Medicine：《新英格兰医学杂志》，创刊于1812年。隶属于美国麻省医学协会，最新IF：70.67

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