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Eflornithine plus Sulindac for Prevention of Progression in Familial Adenomatous Polyposis
- Source :
- New England journal of medicine, 383(11), 1028-1039. Massachussetts Medical Society
- Publication Year :
- 2020
-
Abstract
- 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.).
- Subjects :
- Drug
Oncology
Adult
Male
medicine.medical_specialty
Eflornithine
Combination therapy
media_common.quotation_subject
Kaplan-Meier Estimate
030204 cardiovascular system & hematology
law.invention
Familial adenomatous polyposis
03 medical and health sciences
0302 clinical medicine
Pharmacotherapy
Sulindac
Randomized controlled trial
law
Internal medicine
medicine
Humans
030212 general & internal medicine
media_common
business.industry
General Medicine
medicine.disease
digestive system diseases
Intention to Treat Analysis
Clinical trial
Treatment Outcome
Adenomatous Polyposis Coli
Disease Progression
Drug Therapy, Combination
Female
business
medicine.drug
Subjects
Details
- Language :
- English
- ISSN :
- 00284793
- Database :
- OpenAIRE
- Journal :
- New England journal of medicine, 383(11), 1028-1039. Massachussetts Medical Society
- Accession number :
- edsair.doi.dedup.....70ccbc709a9cc81a7759cdcd49e1444b