RESUMEN
BACKGROUND: Patients with refractory colorectal (CRC) cancer have few treatment options. This trial tests the combination of metformin and irinotecan in this setting. METHODS: A phase 2 single-arm trial was conducted, patients received metformin 2500 mg orally a day plus irinotecan 125 mg/m2 intravenously weekly D1 and D8 every 21 days. The primary endpoint was the disease control rate according to the Response Evaluation Criteria in Solid Tumors version 1.1 at 12 weeks. RESULTS: Between December 2015 and January 2018, 41 patients were enrolled. Seventeen patients (41%) met the primary endpoint of disease control in 12 weeks; hence, the study was deemed positive. The median progression-free survival was 3.3 months (CI 95%, 2.0-4.5 months), and the median overall survival was 8.4 months (CI 95%, 5.9-10.8 months). Both mutation RAS status and disease control at 12 weeks impacted overall survival in the multivariate model (HR 2.28, CI 95%, 1.12-4.7, p = 0.02; and HR 0.21, CI 95%, 0.08-0.5, p = 0.001, respectively). The most common adverse event was diarrhoea (29.2% grade 3). CONCLUSIONS: In this trial, metformin plus irinotecan demonstrated disease control in patients with refractory CRC. Further trials with optimised diarrhoea control are needed to confirm these results.