Effect of Sulidac and Erlotinib vs Placebo on Duodenal Neoplasia in Familial Adenomatous Polyposis

Claire Rummage, Mercer College of Pharmacy


Familial adenomatous polyposis (FAP) is characterized by the development of multiple adenomas in the colon and rectum and eventual colorectal cancer. [1]  The estimated prevalence of FAP is 2.29 to 3.2 cases per 100,000 persons. [2]


The European Society for Medical Oncology (ESMO) recommends secondary chemoprevention with nonsteroidal anti-inflammatory drugs (NSAIDs) such as sulindac or celecoxib in patients with familial adenomatous polyposis. [3]

Effect of Sulidac and Erlotinib vs Placebo on Duodenal Neoplasia in Familial Adenomatous Polyposis [4]
Design Double-blind, placebo-controlled trial; N= 92
Objective To evaluate the effect of combination of sulindac and erlotinib on duodenal adenoma regression in patients with familial adenomatous polyposis (FAP)
Study Groups Sulindac 150 mg twice daily and erlotinib 75 mg daily (n= 46) vs placebo (n= 46)
Methods Eligible participants were either proven carriers of a pathological mutation of the adenomatous polyposis coli (APC) gene or had more than 100 adenomas in the large intestine and were members of a family with FAP.   Participants were randomly assigned in a one to one allocation ratio to either the combination or placebo group for six months. Study drugs were provided to participants and refilled at one to three month intervals.   Drug compliance was assessed through a pill count review of participants’ diaries. Endoscopic evaluations were performed within 30 days before treatment and six months after treatment was initiated.
Duration July 2010 through June 2014
Primary Outcome Measure The change in total polyp burden at six months from baseline
Baseline Characteristics Sulindac-erlotinib (n= 46) Placebo (n= 46)
Age, mean, y 42 41
Male, n 39% 39%
Female, n 61% 61%
FAP status
Classic, n 70% 70%
Attenuated, n 30% 30%
Number of polyps, median 13.5 10.5
Results Duodenal polyp burden (sum of diameters), mm
Baseline, median Six months follow up, median Median change Median change, % net between – group differences p value Net % change

(n= 46)

29.0 19.5 -8.5 -37.9 < 0.001 -71.2

(n= 46)

23.0 31.0 8.0 30.6
Adverse Events Common Adverse Events: rash acneiform (86.9%), oral mucositis (39.1%), diarrhea (26%), nausea (23.9%)
Serious Adverse Events: Grade three from the Common Terminology Criteria for Adverse Events: oral mucostis (2.2%)
Percentage that Discontinued due to Adverse Events: 23.9%
Study Author Conclusions Among participants with FAP, the use of sulindac and erlotinib compared with placebo resulted in a lower duodenal polyp burden after six months.

Although this study showed a lower duodenal polyp burden after the combination therapy, adverse events seen with the sulindac-erlotinib combination may limit the use of these medications. The study was underpowered, needing 100 participates to achieve at 95% power. Therefore, it is less likely to be able to distinguish a true result from coincidence in the study due to the sample size. Also, a longer follow up would help determine if these results turn into improved clinical outcomes.




  1. Cruz-Correa M, Giardiello FM. Familial adenomatous polyposis. Gastrointest Endosc. 2003 Dec;58(6):885-94
  2.  Syngal S, Brand RE, Church JM, Giardiello FM, Hampel HL, Burt RW. American College of Gastroenterology. ACG clinical guideline: Genetic testing and management of hereditary gastrointestinal cancer syndromes. Am J Gastroenterol. 2015 Feb;110(2):223-62.
  3. Balmaña J, Balaguer F, Cervantes A, Arnold D, ESMO Guidelines Working Group. Familial risk-colorectal cancer: ESMO Clinical Practice Guidelines. Ann Oncol. 2013 Oct;24 Suppl 6:vi73-80.
  4. Samadder N, Neklason DW, Boucher KM, et al. Effect of Sulindac and Erlotinib vs Placebo on Duodenal Neoplasia in Familial Adenomatous Polyposis: A Randomized Clinical Trial. JAMA. 2016;315(12):1266-1275. doi:10.1001/jama.2016.2522.

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