Safety and Efficacy of Eflornithine in Patients with Gastric Precancerous Lesions: A Double-blinded, Randomized Clinical Trial

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.