• N Jewel Samadder, Deborah W Neklason, Kenneth M Boucher, Kathryn R Byrne, Priyanka Kanth, Wade Samowitz, David Jones, Sean V Tavtigian, Michelle W Done, Therese Berry, Kory Jasperson, Lisa Pappas, Laurel Smith, Danielle Sample, Rian Davis, Matthew K Topham, Patrick Lynch, Elena Strait, Wendy McKinnon, Randall W Burt, and Scott K Kuwada.
• Huntsman Cancer Institute, University of Utah, Salt Lake City2Department of Medicine (Gastroenterology), University of Utah, Salt Lake City.
• JAMA. 2016 Mar 22; 315 (12): 1266-75.

ImportancePatients 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.ObjectiveTo evaluate the effect of a combination of sulindac and erlotinib on duodenal adenoma regression in patients with FAP.Design, Setting, And ParticipantsDouble-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.InterventionsParticipants 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 Outcomes And MeasuresThe 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 calculated as 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.ResultsNinety-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: see text].Conclusions And RelevanceAmong 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.Trial Registrationclinicaltrials.gov Identifier: NCT 01187901.

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