Safety and Efficacy of Eflornithine in Patients with Gastric Precancerous Lesions: A Double-blinded, Randomized Clinical Trial
Mené sur 91 patients présentant une atrophie gastrique ou une métaplasie gastro-intestinale (âge moyen : 45,2 ans ; 74 % de femmes), cet essai randomisé de phase IIa évalue la sécurité et l'efficacité de l'éflornithine pour prévenir le risque de cancer de l'estomac
Gastric adenocarcinoma (GC) is the fifth leading cause of global cancer mortality and a major health disparity in the U.S. Effective chemoprevention strategies are limited for high-risk individuals with gastric premalignant conditions (GPMC). We conducted an NCI-DCP-funded, double-blind, Phase IIa randomized, placebo-controlled trial evaluating eflornithine for chemoprevention in GPMC (NCT02794428). The study was executed in rural Honduras and Puerto Rico, regions with a high prevalence of H. pylori (Hp) and gastric intestinal metaplasia (GIM), from September 2016 to December 2022. Eligible subjects (ages 30-69; Hp-positive or Hp-negative) were randomized 1:1 to receive 500 mg/day eflornithine or placebo for 18 months. Upper endoscopy was performed at baseline, 6, 18, and 24 months. Hp-positive patients were offered antibiotic treatment at 6 months. A total of 211 patients were screened, and 91 randomized (45 eflornithine, 46 placebo). The mean age was 45.2 years (SD 8.8), and 74% were female. At baseline, 46% and 54% had gastric atrophy and GIM, respectively. 80% were Hp-positive. Follow-up completion rates were 78 (6 months), 69 (18 months), and 55 (24 months) patients. Eflornithine was well tolerated, with fewer grade 1-2 adverse events in the eflornithine group (81 vs. 108, placebo). No significant histology score differences were observed. A significant reduction in DNA damage (pH2AX-positive cells) was observed in the 24-month versus 18-month assessments (P = 0.012). Eflornithine was safe and well tolerated in patients with GPMC. The findings suggest that eflornithine reduces long-term DNA damage, supporting further trials to refine treatment duration and patient selection.
Cancer Prevention Research , résumé, 2026