Adjuvant S-1 Plus Metformin after Pancreatic Cancer Resection: A Multicenter Randomized Phase II Trial
Abstract
Abstract Background Six months of adjuvant S-1 is the standard treatment for resected pancreatic cancer in Japan. Metformin has demonstrated potential anticancer effects in preclinical and observational studies. This study aimed to evaluate whether adding metformin to S-1 improves 2-year survival after pancreatic cancer resection. Methods This multicenter, randomized, open-label Phase II trial enrolled patients with histologically confirmed Stage I–II invasive pancreatic ductal carcinoma who underwent curative resection. Patients were randomized to receive S-1 plus metformin (Group A) or S-1 alone (Group B). S-1 was administered for 6 months in both groups, and metformin for 2 years in Group A. The primary endpoint was 2-year overall survival; secondary endpoints were recurrence-free survival and safety. The sample size was calculated assuming a 2-year survival rate of 65% with S-1 alone and 78% with S-1 plus metformin (hazard ratio: 0.58), providing 80% power with a one-sided α of 0.20. Glycemia-related safety was monitored using Common Terminology Criteria for Adverse Events-defined hyperglycemia and hypoglycemia. Results Seventy-six patients were randomized (38 per group). The 2-year survival rate was 66.7% in Group A and 66.1% in Group B (hazard ratio 1.09; 95% confidence interval 0.55–2.16; p = 0.93). Median overall survival was 53.8 versus 58.0 months, and median recurrence-free survival was 17.9 versus 12.6 months ( p = 0.78). No grade ≥ 4 adverse events occurred;…
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Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 2 of 5 (High · randomized trial). Randomized trials of a reasonable size are the strongest single-study design.
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