title: Effect of Sulindac and Erlotinib vs Placebo on Duodenal Neoplasia in Familial Adenomatous Polyposis: A Randomized Clinical Trial.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  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 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.
  
  
  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: see text].
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT 01187901.
authors.affiliation: Huntsman Cancer Institute, University of Utah, Salt Lake City2Department of Medicine (Gastroenterology), University of Utah, Salt Lake City.
authors.forename: N Jewel
authors.initials: NJ
authors.lastname: Samadder
authors.affiliation: Huntsman Cancer Institute, University of Utah, Salt Lake City3Department of Oncological Sciences, University of Utah, Salt Lake City4Department of Medicine (Genetic Epidemiology), University of Utah, Salt Lake City.
authors.forename: Deborah W
authors.initials: DW
authors.lastname: Neklason
authors.affiliation: Huntsman Cancer Institute, University of Utah, Salt Lake City5Department of Medicine (Epidemiology), University of Utah, Salt Lake City.
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Boucher
authors.affiliation: Department of Medicine (Gastroenterology), University of Utah, Salt Lake City.
authors.forename: Kathryn R
authors.initials: KR
authors.lastname: Byrne
authors.affiliation: Department of Medicine (Gastroenterology), University of Utah, Salt Lake City.
authors.forename: Priyanka
authors.initials: P
authors.lastname: Kanth
authors.affiliation: Huntsman Cancer Institute, University of Utah, Salt Lake City6Department of Pathology, University of Utah, Salt Lake City.
authors.forename: Wade
authors.initials: W
authors.lastname: Samowitz
authors.affiliation: Huntsman Cancer Institute, University of Utah, Salt Lake City3Department of Oncological Sciences, University of Utah, Salt Lake City.
authors.forename: David
authors.initials: D
authors.lastname: Jones
authors.affiliation: Huntsman Cancer Institute, University of Utah, Salt Lake City3Department of Oncological Sciences, University of Utah, Salt Lake City.
authors.forename: Sean V
authors.initials: SV
authors.lastname: Tavtigian
authors.affiliation: Huntsman Cancer Institute, University of Utah, Salt Lake City.
authors.forename: Michelle W
authors.initials: MW
authors.lastname: Done
authors.affiliation: Huntsman Cancer Institute, University of Utah, Salt Lake City.
authors.forename: Therese
authors.initials: T
authors.lastname: Berry
authors.affiliation: Huntsman Cancer Institute, University of Utah, Salt Lake City.
authors.forename: Kory
authors.initials: K
authors.lastname: Jasperson
authors.affiliation: Huntsman Cancer Institute, University of Utah, Salt Lake City.
authors.forename: Lisa
authors.initials: L
authors.lastname: Pappas
authors.affiliation: Huntsman Cancer Institute, University of Utah, Salt Lake City.
authors.forename: Laurel
authors.initials: L
authors.lastname: Smith
authors.affiliation: Huntsman Cancer Institute, University of Utah, Salt Lake City.
authors.forename: Danielle
authors.initials: D
authors.lastname: Sample
authors.affiliation: Huntsman Cancer Institute, University of Utah, Salt Lake City.
authors.forename: Rian
authors.initials: R
authors.lastname: Davis
authors.affiliation: Huntsman Cancer Institute, University of Utah, Salt Lake City3Department of Oncological Sciences, University of Utah, Salt Lake City7Department of Medicine (Pulmonary), University of Utah, Salt Lake City.
authors.forename: Matthew K
authors.initials: MK
authors.lastname: Topham
authors.affiliation: Department of Gastroenterology, University of Texas MD Anderson Cancer Center, Houston.
authors.forename: Patrick
authors.initials: P
authors.lastname: Lynch
authors.affiliation: Penrose Hospital, Colorado Springs, Colorado.
authors.forename: Elena
authors.initials: E
authors.lastname: Strait
authors.affiliation: University of Vermont Cancer Center, Burlington.
authors.forename: Wendy
authors.initials: W
authors.lastname: McKinnon
authors.affiliation: Huntsman Cancer Institute, University of Utah, Salt Lake City2Department of Medicine (Gastroenterology), University of Utah, Salt Lake City3Department of Oncological Sciences, University of Utah, Salt Lake City.
authors.forename: Randall W
authors.initials: RW
authors.lastname: Burt
authors.affiliation: Department of Medicine, University of Hawaii, Honolulu.
authors.forename: Scott K
authors.initials: SK
authors.lastname: Kuwada
mesh_terms: D011125:Adenomatous Polyposis Coli / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D000328:Adult; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D004379:Duodenal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D000069347:Erlotinib Hydrochloride / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D017491:Genes, APC; D006801:Humans; D008297:Male; D008875:Middle Aged; D013467:Sulindac / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D000970:Antineoplastic Agents; D013467:Sulindac; D000069347:Erlotinib Hydrochloride