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JAMA Oncol. 2018 May 1;4(5):671-677. doi: 10.1001/jamaoncol.2017.5431.

Association of Sulindac and Erlotinib vs Placebo With Colorectal Neoplasia in Familial Adenomatous Polyposis: Secondary Analysis of a Randomized Clinical Trial.

Author information

1
Huntsman Cancer Institute, The University of Utah, Salt Lake City.
2
Department of Medicine (Gastroenterology), The University of Utah, Salt Lake City.
3
Division of Gastroenterology and Hepatology, Mayo Clinic, Scottsdale, Arizona.
4
Department of Medicine, University of Hawaii, Honolulu.
5
Department of Medicine (Epidemiology), The University of Utah, Salt Lake City.
6
Department of Pathology, The University of Utah, Salt Lake City.
7
Department of Oncological Sciences, The University of Utah, Salt Lake City.
8
Department of Medicine (Genetic Epidemiology), The University of Utah, Salt Lake City.

Abstract

Importance:

Patients with familial adenomatous polyposis (FAP) are at markedly increased risk for colorectal polyps and cancer. A combination of sulindac and erlotinib led to a 71% reduction in duodenal polyp burden in a phase 2 trial.

Objective:

To evaluate effect of sulindac and erlotinib on colorectal adenoma regression in patients with FAP.

Design, Setting, and Participants:

Prespecified secondary analysis for colorectal adenoma regression was carried out using data from a double-blind, randomized, placebo-controlled trial, enrolling 92 patients with FAP, conducted from July 2010 to June 2014 in Salt Lake City, Utah.

Interventions:

Patients 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 Measurements:

The total number of polyps in the intact colorectum, ileal pouch anal anastomosis, or ileo-rectum were recorded at baseline and 6 months. The primary outcomes were change in total colorectal polyp count and percentage change in colorectal polyps, following 6 months of treatment.

Results:

Eighty-two randomized patients (mean [SD] age, 40 [13] years; 49 [60%] women) had colorectal polyp count data available for this secondary analysis: 22 with intact colon, 44 with ileal pouch anal anastomosis and 16 with ileo-rectal anastomosis; 41 patients received sulindac/erlotinib and 41 placebo. The total colorectal polyp count was significantly different between the placebo and sulindac-erlotinib group at 6 months in patients with net percentage change of 69.4% in those with an intact colorectum compared with placebo (95% CI, 28.8%-109.2%; P = .009).

Conclusion and Relevance:

In this double-blind, placebo-controlled, randomized trial we showed that combination treatment with sulindac and erlotinib compared with placebo resulted in significantly lower colorectal polyp burden after 6 months of treatment. There was a reduction in polyp burden in both those with an entire colorectum and those with only a rectal pouch or rectum.

Trial Registration:

clinicaltrials.gov Identifier: NCT01187901.

PMID:
29423501
PMCID:
PMC5885170
DOI:
10.1001/jamaoncol.2017.5431

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