BACKGROUND: The efficacy and safety of combination therapy with eflornithine and 
sulindac, as compared with either drug alone, in delaying disease progression in 
patients with familial adenomatous polyposis are unknown.
METHODS: We evaluated the efficacy and safety of the combination of eflornithine 
and sulindac, as compared with either drug alone, in adults with familial 
adenomatous polyposis. The patients were stratified on the basis of anatomical 
site with the highest polyp burden and surgical status; the strata were 
precolectomy (shortest projected time to disease progression), rectal or ileal 
pouch polyposis after colectomy (longest projected time), and duodenal polyposis 
(intermediate projected time). The patients were then randomly assigned in a 
1:1:1 ratio to receive 750 mg of eflornithine, 150 mg of sulindac, or both once 
daily for up to 48 months. The primary end point, assessed in a time-to-event 
analysis, was disease progression, defined as a composite of major surgery, 
endoscopic excision of advanced adenomas, diagnosis of high-grade dysplasia in 
the rectum or pouch, or progression of duodenal disease.
RESULTS: A total of 171 patients underwent randomization. Disease progression 
occurred in 18 of 56 patients (32%) in the eflornithine-sulindac group, 22 of 58 
(38%) in the sulindac group, and 23 of 57 (40%) in the eflornithine group, with 
a hazard ratio of 0.71 (95% confidence interval [CI], 0.39 to 1.32) for 
eflornithine-sulindac as compared with sulindac (P = 0.29) and 0.66 (95% CI, 
0.36 to 1.24) for eflornithine-sulindac as compared with eflornithine. Among 37 
precolectomy patients, the corresponding values in the treatment groups were 2 
of 12 patients (17%), 6 of 13 (46%), and 5 of 12 (42%) (hazard ratios, 0.30 [95% 
CI, 0.07 to 1.32] and 0.20 [95% CI, 0.03 to 1.32]); among 34 patients with 
rectal or ileal pouch polyposis, the values were 4 of 11 patients (36%), 2 of 11 
(18%), and 5 of 12 (42%) (hazard ratios, 2.03 [95% CI, 0.43 to 9.62] and 0.84 
[95% CI, 0.24 to 2.90]); and among 100 patients with duodenal polyposis, the 
values were 12 of 33 patients (36%), 14 of 34 (41%), and 13 of 33 (39%) (hazard 
ratios, 0.73 [95% CI, 0.34 to 1.52] and 0.76 [95% CI, 0.35 to 1.64]). Adverse 
and serious adverse events were similar across the treatment groups.
CONCLUSIONS: In this trial involving patients with familial adenomatous 
polyposis, the incidence of disease progression was not significantly lower with 
the combination of eflornithine and sulindac than with either drug alone. 
(Funded by Cancer Prevention Pharmaceuticals; ClinicalTrials.gov number, 
NCT01483144; EudraCT number, 2012-000427-41.).