Format

Send to

Choose Destination
JAMA. 2016 Mar 22-29;315(12):1266-75. doi: 10.1001/jama.2016.2522.

Effect of Sulindac and Erlotinib vs Placebo on Duodenal Neoplasia in Familial Adenomatous Polyposis: A Randomized Clinical Trial.

Author information

1
Huntsman Cancer Institute, University of Utah, Salt Lake City2Department of Medicine (Gastroenterology), University of Utah, Salt Lake City.
2
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.
3
Huntsman Cancer Institute, University of Utah, Salt Lake City5Department of Medicine (Epidemiology), University of Utah, Salt Lake City.
4
Department of Medicine (Gastroenterology), University of Utah, Salt Lake City.
5
Huntsman Cancer Institute, University of Utah, Salt Lake City6Department of Pathology, University of Utah, Salt Lake City.
6
Huntsman Cancer Institute, University of Utah, Salt Lake City3Department of Oncological Sciences, University of Utah, Salt Lake City.
7
Huntsman Cancer Institute, University of Utah, Salt Lake City.
8
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.
9
Department of Gastroenterology, University of Texas MD Anderson Cancer Center, Houston.
10
Penrose Hospital, Colorado Springs, Colorado.
11
University of Vermont Cancer Center, Burlington.
12
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.
13
Department of Medicine, University of Hawaii, Honolulu.

Abstract

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 OUTCOMES AND 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 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 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.

TRIAL REGISTRATION:

clinicaltrials.gov Identifier: NCT 01187901.

PMID:
27002448
PMCID:
PMC5003411
DOI:
10.1001/jama.2016.2522
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Samadder reports being a consultant for Cook Medical. Dr Jasperson reports being an employee of Ambry Genetics. Dr Burt reports being a consultant for Myriad Genetics and receiving personal fees from Thetis Pharmaceuticals. No other disclosures were reported.

Supplemental Content

Full text links

Icon for Silverchair Information Systems Icon for PubMed Central
Loading ...
Support Center