Dual therapy of eflornithine and sulindac was not more effective at treating patients with familial adenomatous polyposis than either drug alone. These findings, from a randomized clinical trial, were published in The New England Journal of Medicine.
Adult patients (N=171) with clinical familial adenomatous polyposis who had pathogenic variants of adenomatous polyposis coli (APC) were recruited. Patients were randomly assigned in a 1:1:1 ratio to receive 750 mg eflornithine (n=57), 150 mg sulindac (n=58), or both (n=56) daily for up to 48 months. Patients in the monotherapy groups received a placebo for the other drug. Patients were assessed for disease progression.
Disease progression occurred among 40% of the eflornithine group, 38% of the sulindac group, and 32% of the dual therapy group. Progression was observed in the form of lower gastrointestinal polyposis, duodenal polyposis, and progression to Spigelman stage.
The estimated average time to first event of disease progression was 21.8 (95% CI, 21.4-22.2), 23.6 (95% CI, 23.2-23.9), and 32.3 (95% CI, 31.8-32.8) months for the eflornithine, sulindac, and dual therapy groups, respectively.
Compared with the dual therapy group, patients treated with eflornithine or sulindac alone were not at increased risk for disease progression (hazard ratio [HR], 0.66; 95% CI, 0.36-1.22 and HR, 0.71; 95% CI, 0.39-1.32, respectively).
Risk for disease progression among patients who required a precolectomy or duodenal polyposis was similar for eflornithine or sulindac treatment cohorts compared with the dual therapy group. Risk for disease progression was elevated among patients who required rectal or ileal pouch polyposis and who received sulindac therapy (HR, 2.03; 95% CI, 0.43-9.62) but not among those receiving eflornithine (HR, 0.84; 95% CI, 0.24-2.90).
Adverse events were reported by a majority of patients in all treatment groups (eflornithine: 55% vs sulindac: 74% vs dual therapy: 68%). Most adverse events were minor (nausea, headache, diarrhea, vomiting, rectal hemorrhage, abdominal pain, flatulence, dyspepsia, and altered appetite). A total of 20 participants discontinued treatment due to adverse events.
This study was limited by its small sample size which caused the 95% confidence intervals to be wide.
The conclusions made on the basis of these data were that dual therapy with eflornithine and sulindac did not improve clinical outcomes or disease progression than either drug alone. However, the investigators asserted that further studies were needed with larger sample sizes to better investigate the dual therapy’s effect in the lower gastrointestinal tract, as none of the dual therapy recipients with an intact colon at baseline required surgical intervention during the study. This observation may indicate there is a patient population in which the dual therapy may be beneficial.
Disclosure: This clinical trial was supported by Cancer Prevention Pharmaceuticals. Please see the original reference for a full list of authors’ disclosures.
Burke CA, Dekker E, Lynch P, et al. Eflornithine plus sulindac for prevention of progression in familial adenomatous polyposis. N Engl J Med. 2020;383(11):1028-1039.