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

welcome to oneFAPvoice

- a positively charged Familial Adenomatous Polyposis community.
  • join today!
scientific articles

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

key information

source: JAMA

year: 2016

authors: Samadder NJ, Neklason DW, Boucher KM, Byrne KR, Kanth P, Samowitz W, Jones D, Tavtigian SV, Done MW, Berry T, Jasperson K, Pappas L, Smith L, Sample D, Davis R, Topham MK, Lynch P, Strait E, McKinnon W, Burt RW, Kuwada SK

summary/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.

organization: Huntsman Cancer Institute, MD Anderson Cancer Center, Penrose Hospital, University of Vermont Cancer Center, University of Hawaii

DOI: 10.1001/jama.2016.2522

read more full text source

expertly curated content related to this topic

To improve your experience on this site, we use cookies. This includes cookies essential for the basic functioning of our website, cookies for analytics purposes, and cookies enabling us to personalize site content. By clicking on 'Accept' or any content on this site, you agree that cookies can be placed. You may adjust your browser's cookie settings to suit your preferences.
More information

The cookie settings on this website are set to "allow cookies" to give you the best browsing experience possible. If you continue to use this website without changing your cookie settings or you click "Accept" below then you are consenting to this.

Close