Combination therapy with sulindac and erlotinib reduced duodenal polyp burden in patients with familial adenomatous polyposis, according to the results of a double blind, randomized, placebo-controlled trial.
“Multiple studies have shown that the cyclooxygenase (COX) inhibitor, sulindac ... significantly inhibits colorectal adenomatous polyps in patients with FAP; however, NSAIDs have much less efficacy in duodenal adenomas,” the researchers wrote. “Celecoxib use resulted in a modest reduction of duodenal and colorectal polyps, but is no longer [FDA]-approved for this indication, due to lack of complete follow-up studies.”
Furthermore, results from a mouse model showing sulindac combined with an epidermal growth factor receptor inhibitor reduced small intestinal adenoma development, led the researchers to hypothesize that this combination would reduce duodenal adenoma formation in patients with FAP.
Thus, from July 2010 through June 2014 at the Huntsman Cancer Center Institute in Salt Lake City, Utah, the researchers randomly assigned 92 patients with FAP (mean age, 41 years; range, 24-55 years; 61% women) to receive 150 mg sulindac twice daily and 75 mg erlotinib daily (n = 46) or placebo (n = 46) for 6 months.
After these 92 patients were enrolled, “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,” the researchers wrote.
The researchers endoscopically assessed the number and diameter of polyps in the proximal duodenum at 6 months, and change in total polyp burden at this time point served as the primary endpoint.
Treatment was well tolerated, and the treatment group had more grade 1 and 2 adverse events; an acne-like rash occurred in 87% vs. 20% with placebo (P < .001). Grade 3 adverse events occurred in two participants.
The median change in duodenal polyp burden at 6 months was –8.5 mm in the treatment group vs. 8 mm in the placebo group, for a between-group difference of –19 mm (95% CI; –32 to –10.9; P < .001). Median change in duodenal polyp count at 6 months was also significantly different between groups (–8; 95% CI, –12.2 to –4.7; P < .001).
“Among participants with FAP, the use of sulindac and erlotinib compared with placebo resulted in a lower duodenal polyp burden after 6 months,” the researchers concluded. “However, the frequency of adverse events may limit the use of these medications at the doses used in this study. Further researcher 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.” – by Adam Leitenberger
Disclosure: Samadder reports being a consultant for Cook Medical. Please see the full study for a list of all other researchers’ relevant financial disclosures.