Combination therapy does not reduce progression of familial adenomatous polyposis
For patients with familial adenomatous polyposis, incidence of disease progression was not significantly lower with combination eflornithine and sulindac compared with either drug alone, according to recently published results.
“While the study found that overall progression of FAP related events did not differ between the arms of the study, the compelling finding was that no patient in the eflornithine-sulindac combination arm required colectomy, proctectomy or resection of the ileal pouch over the 48 months of the study, which was not the case in the sulindac alone or eflorinithine alone arms,” Carol Burke, MD, director of the Center for Colon Polyp and Cancer Prevention and head of the section of polyposis in the Sanford R. Weiss, MD, Center for Hereditary Colorectal Neoplasia at Cleveland Clinic, told Healio Gastroenterology. “Clinicians look forward to safe and effective therapy for lower gastrointestinal polyposis control in patients with FAP and would welcome the ability to combine sulindac with eflornithine to manage select patients who need it.”
Burke and colleagues randomly assigned 171 adults with familial adenomatous polyposis 1:1:1 to receive 750 mg of eflornithine (n = 57), 150 mg of sulindac (n = 58) or both (n = 56) once daily for up to 48 months. Investigators stratified patients based on 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). Disease progression served as the primary endpoint, which researchers evaluated in a time-to-event analysis.
Results showed disease progression occurred in 18 patients who received both treatments, 22 patients in the sulindac group and 23 patients in the eflornithine group. Investigators reported a hazard ratio of 0.71 (95% CI, 0.39-1.32) for eflornithine–sulindac vs. sulindac (P = .29) and 0.66 (95% CI, 0.36-1.23) for eflornithine–sulindac vs. eflornithine. For the 37 patients who underwent precolectomy, the corresponding values in the treatment groups were two patients from the eflornithine–sulindac group, six patients in the sulindac group and five patients in the eflornithine group (HR = 0.3; 95% CI, 0.07-1.32 and HR = 0.2; 95% CI, 0.03-1.32). Among the 34 patients with rectal or ileal pouch polyposis, those values were four patients in the eflornithine–sulindac group, two patients in the sulindac group and five patients in the eflornithine group (HR = 2.03; 95% CI, 0.43-9.62 and HR = 0.84; 95% CI, 0.24-2.9). In the 100 patients with duodenal polyposis, the values were 12 in the eflornithine–sulindac group, 14 patients in the sulindac group and 13 patients in the eflornithine group (HR = 0.72; 95% CI, 0.34-1.52 and HR = 0.76; 95% CI, 0.35-1.64). All treatment groups experienced similar adverse and serious adverse events.
“Our trial did not show that the incidence of disease progression was significantly lower with the combination of eflornithine and sulindac than with either drug alone,” Burke and colleagues concluded.