TY - JOUR
T1 - Effect of sulindac and erlotinib vs placebo
T2 - On duodenal neoplasia in familial adenomatous polyposis: A randomized clinical trial
AU - Samadder, N. Jewel
AU - Neklason, Deborah W.
AU - Boucher, Kenneth M.
AU - Byrne, Kathryn R.
AU - Kanth, Priyanka
AU - Samowitz, Wade
AU - Jones, David
AU - Tavtigian, Sean V.
AU - Done, Michelle W.
AU - Berry, Therese
AU - Jasperson, Kory
AU - Pappas, Lisa
AU - Smith, Laurel
AU - Sample, Danielle
AU - Davis, Rian
AU - Topham, Matthew K.
AU - Lynch, Patrick
AU - Strait, Elena
AU - McKinnon, Wendy
AU - Burt, Randall W.
AU - Kuwada, Scott K.
N1 - Funding Information:
Funding/Support: This project was funded by provided by grant P01-CA073992 from the National Cancer Institute (Drs Burt and Tavtigian); the Huntsman Cancer Institute Cancer Center Support Grant (NCI P30CA042014), as well as by the Huntsman Cancer Foundation; by a junior faculty career development award from the American College of Gastroenterology (Dr Samadder); and by grant 1ULTR001067 from the National Institutes of Health National Center for Advancing Translational Sciences.
Publisher Copyright:
Copyright 2016 American Medical Association. All rights reserved.
PY - 2016/3/22
Y1 - 2016/3/22
N2 - IMPORTANCE: Patients with familial adenomatous polyposis (FAP) are at markedly increased risk for duodenal polyps and cancer. Surgical and endoscopic management of duodenal neoplasia is difficult and chemoprevention has not been successful. OBJECTIVE: To evaluate the effect of a combination of sulindac and erlotinib on duodenal adenoma regression in patients with FAP. DESIGN, SETTING, AND PARTICIPANTS: Double-blind, randomized, placebo-controlled trial, enrolling 92 participants with FAP, conducted from July 2010 through June 2014 at Huntsman Cancer Institute in Salt Lake City, Utah. INTERVENTIONS: Participants with FAP were randomized to sulindac (150 mg) twice daily and erlotinib (75 mg) daily (n = 46) vs placebo (n = 46) for 6 months. MAIN OUTCOMESAND MEASURES: The total number and diameter of polyps in the proximal duodenum were mapped at baseline and 6 months. The primary outcome was change in total polyp burden at 6 months. Polyp burden was calculatedas the sum of the diameters of polyps. The secondary outcomes were change in total duodenal polyp count, change in duodenal polyp burden or count stratified by genotype and initial polyp burden, and percentage of change from baseline in duodenal polyp burden. RESULTS: Ninety-two participants (mean age, 41 years [range, 24-55]; women, 56 [61%]) were randomized when the trial was stopped by the external data and safety monitoring board because the second preplanned interim analysis met the prespecified stopping rule for superiority. Grade 1 and 2 adverse events were more common in the sulindac-erlotinib group, with an acne-like rash observed in 87% of participants receiving treatment and 20% of participants receiving placebo (P <.001). Only 2 participants experienced grade 3 adverse events. (Table presented) CONCLUSIONS AND RELEVANCE: Among participants with FAP, the use of sulindac and erlotinib compared with placebo resulted in a lower duodenal polyp burden after 6 months. Adverse events may limit the use of these medications at the doses used in this study. Further research is necessary to evaluate these preliminary findings in a larger study population with longer follow-up to determine whether the observed effects will result in improved clinical outcomes.
AB - IMPORTANCE: Patients with familial adenomatous polyposis (FAP) are at markedly increased risk for duodenal polyps and cancer. Surgical and endoscopic management of duodenal neoplasia is difficult and chemoprevention has not been successful. OBJECTIVE: To evaluate the effect of a combination of sulindac and erlotinib on duodenal adenoma regression in patients with FAP. DESIGN, SETTING, AND PARTICIPANTS: Double-blind, randomized, placebo-controlled trial, enrolling 92 participants with FAP, conducted from July 2010 through June 2014 at Huntsman Cancer Institute in Salt Lake City, Utah. INTERVENTIONS: Participants with FAP were randomized to sulindac (150 mg) twice daily and erlotinib (75 mg) daily (n = 46) vs placebo (n = 46) for 6 months. MAIN OUTCOMESAND MEASURES: The total number and diameter of polyps in the proximal duodenum were mapped at baseline and 6 months. The primary outcome was change in total polyp burden at 6 months. Polyp burden was calculatedas the sum of the diameters of polyps. The secondary outcomes were change in total duodenal polyp count, change in duodenal polyp burden or count stratified by genotype and initial polyp burden, and percentage of change from baseline in duodenal polyp burden. RESULTS: Ninety-two participants (mean age, 41 years [range, 24-55]; women, 56 [61%]) were randomized when the trial was stopped by the external data and safety monitoring board because the second preplanned interim analysis met the prespecified stopping rule for superiority. Grade 1 and 2 adverse events were more common in the sulindac-erlotinib group, with an acne-like rash observed in 87% of participants receiving treatment and 20% of participants receiving placebo (P <.001). Only 2 participants experienced grade 3 adverse events. (Table presented) CONCLUSIONS AND RELEVANCE: Among participants with FAP, the use of sulindac and erlotinib compared with placebo resulted in a lower duodenal polyp burden after 6 months. Adverse events may limit the use of these medications at the doses used in this study. Further research is necessary to evaluate these preliminary findings in a larger study population with longer follow-up to determine whether the observed effects will result in improved clinical outcomes.
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U2 - 10.1001/jama.2016.2522
DO - 10.1001/jama.2016.2522
M3 - Article
C2 - 27002448
AN - SCOPUS:84962327352
SN - 0098-7484
VL - 315
SP - 1266
EP - 1275
JO - JAMA - Journal of the American Medical Association
JF - JAMA - Journal of the American Medical Association
IS - 12
ER -