For patients with FAP, surgery and endoscopic management of duodenal neoplasia is difficult and chemoprevention has not always proved successful, report study authors from Salt Lake City, UT. To evaluate the effect of combination sulindac and erolitinib on duodenal adenoma regression in these patients, the team conducted a double-blind, randomized, placebo-controlled trial (n=92) from July 2010–June 2014. Patients were randomized to sulindac 150mg twice daily and erlotinib 75mg daily or placebo for 6 months.
The primary outcome was change in total polyp burden at 6 months, 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, and percentage of change from baseline in duodenal polyp burden.
The trial was stopped prematurely by recommendation of an external data and safety monitoring board because the second interim analysis met the prespecified stopping rule for superiority. The median duodenal polyp burden in the sulindac/erlotinib group decreased –8.5mm (from 29.0mm to 19.5mm) vs. an 8.0mm increase (from 23.0mm to 31.0mm) seen in the placebo group (net difference –19.0mm, 95% CI: –32.0 to –10.9; P<0.001).
The median duodenal polyp count decreased from 13.5 to 10.0 in the sulindac/erlotinib group vs. an increase from 10.5 to 17.0 in the placebo group (net difference –8.0 polyps, 95% CI: –12.2 to –4.7; P<0.001).
Study authors also noted that “adverse events may limit the use of these medications at the doses used in this study.” Eighty-seven percent of patients taking the combination experienced acne-like rash compared with 20% in the placebo group. More research is needed to evaluate these initial findings in a larger cohort with longer follow-up.
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