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©The Author(s) 2021.
World J Gastroenterol. May 7, 2021; 27(17): 1883-1904
Published online May 7, 2021. doi: 10.3748/wjg.v27.i17.1883
Published online May 7, 2021. doi: 10.3748/wjg.v27.i17.1883
Table 2 Selected clinical studies of metformin on digestive system cancers treatment
Ref. | Study design and population | Inclusion criteria | Combined interventions /drugs | Main findings |
Colorectal cancer | ||||
Ramjeesingh et al[99], 2016 | Retrospective cohort. 1394 all stages CRC patients | Patients with CRC | Metformin user vs nonuser | HR: 0.81 (0.60-1.08) |
Skinner et al[100], 2013 | Retrospective cohort. 482 locally rectal cancer patients | Locally advanced rectal adenocarcinoma treated with chemoradiation and surgery | Metformin user vs nonuser | pCR: OR: 16.8 (1.6-181.1). OS at 5 and 10 years (metformin vs non): 81% and 79% vs 56% and 39% (P = 0.022) |
Miranda et al[101], 2016 | Phase 2 Clinical trial. 50 refractory CRC patients | Refractory CRC patients | Metformin 850 mg twice a day+ 5-FU 425 mg/m2 weekly | PFS: 1.8 mo. OS: 7.9 mo. Obese vs lean: 12.4 vs 5.8 mo |
Bragagnoli et al[102], 2021 | Phase 2 Clinical trial, 41 refractory CRC patients | Refractory CRC patients | Metformin 2500 mg a day+ Irinotecan 125 mg/m2 D1, D8, every 21 d | PFS: 2.4 mo, CI 95%, 2.0-4.5 mo. OS: 8.4 mo, CI 95%, 5.9-10.8 mo |
El-Fatatry et al[103], 2018 | Clinical Trial, 40 Stage III CRC patients | Stage III CRC patients | FOLFOX 4 12 cycles + metformin 500 mg 3 times a day | Neuropathy grade 2-3 (metformin vs non): 60% vs 95% (P = 0.009) |
Gastric cancer | ||||
Lee et al[118], 2016 | Retrospective Cohort, single center in Korea. 1974 GC resected patients: – 132 DM2 with metformin; –192 DM2 without metformin; –1648 non-diabetic | GC patients who underwent curative gastrectomy | Metformin user vs nonuser | OS-HR: 0.58 (0.37-0.93). RFS-HR: 0.63 (0.41-0.98) |
Lacroix et al[120], 2018 | Retrospective Cohort. 371 Patients | Stage I to III GC patients | Metformin user vs nonuser | OS-HR: 0.73 (0.52-1.01); cancer specific mortality-HR: 0.86 (0.56-1.33) |
Baglia et al[121], 2019 | Prospective cohort study in Shangai. 543 GC patients | Breast, CRC, lung and GC patients | Metformin user vs nonuser | OS-HR: 1.11 (0.81-1.53). Disease-specific survival-HR: 1.03 (0.73-1.43) |
Seo et al[119], 2019 | Retrospective cohort study. 2187 GC resected patients: – 103 DM2 with metformin; –139 DM2 without metformin; –1945 non-diabetic | GC patients who underwent curative gastrectomy | Metformin user vs nonuser | HR: 0.45 (0.30-0.66) |
PDAC | ||||
Sadeghi et al[128], 2012 | Retrospective cohort. n = 302 | DM2 patients. All stages. United States single center | Metformin user vs nonuser | HR: 0.64 (0.48-0.86) |
Chaiteerakij et al[129], 2016 | Retrospective cohort. n = 980 | DM2 patients. All stages. United States single center | Metformin user vs nonuser | HR: 0.93 (0.81-1.07) |
Lee et al[133], 2016 | Retrospective cohort. n = 237 | DM2 patients. All stages. Korean single center | Use of metformin ≥ 1-mo post-diagnosis vs nonuser | HR: 0.61 (0.46-0.81) |
Ambe et al[130], 2016 | Prospective cohort study n = 44 | DM2 patients. Resected PDAC, stage I-II. United States single center | Metformin user vs nonuser | HR: 0.54 (0.16-1.86) |
Cerullo et al[131], 2016 | Retrospective cohort. n = 3393 | Resected PDAC United States population based | Metformin use after surgery vs nonuser | HR: 0.79 (0.67-0.93) |
Jang et al[132], 2017 | Prospective cohort. n = 764 | DM2, OHA user. Resected Korean population based | Metformin user vs nonuser | HR: 0.73 (0.61-0.87) |
Hwang et al[135], 2013 | Retrospective cohort. n = 516 | DM2 patients. Locally advanced and metastatic. United Kingdom population based | Use of metformin peridiagnosis vs nonuser | HR: 1.11 (0.89-1.38) |
Choi et al[134], 2016 | Retrospective cohort. n = 183 | DM2 patients. Locally advanced and metastatic. Korean single center | Metformin user vs nonuser | HR: 0.69 (0.49-0.97) |
Kordes et al[137], 2015 | RCT, n = 121 | Locally advanced and metastatic. Multicentric. Netherlands | Gemcitabine-everolimus (1000 mg/m2 D1, 8, 15-every 28 d-1.000 mg/d) +/- metformin (2000 mg/d) | HR: 1.05 (0.72-1.55) |
Reni et al[138], 2016 | RCT. n = 60 | Metastatic. Single center. Italian | PEXG (cisplatin-epirubicin-capecitabine-gemcitabine: 30 mg/m2 D1,14- 30 mg/m2 D1,14-2500 mg/m2 D1–28 – 800 mg/m2 D1–14) +/- metformin 2000 mg/d | HR: 1.56 (0.87-2.80) |
Zhou et al[136], 2017 | Meta-analysis12 cohort studies and 2 RCT. n = 94778 | Studies that investigated metformin exposition. All stages PDAC | Metformin user vs nonuser | HR: 0.77 (0.68-0.87) |
Li et al[139], 2017 | Meta-analysis. 9 cohort study and 2 RCT. n = 8089 | Studies that investigated metformin exposition. All stages PDAC | Metformin user vs nonuser | HR: 0.86 (0.76-0.97) |
Wan et al[140], 2018 | Meta-analysis 15 cohort studies and 2 RCT, n = 36791 | Studies that investigated metformin exposition. All stages PDAC | Metformin user vs nonuser | HR: 0.88 (0.80-0.97). Asians only HR: 0.74 (0.58-0.94); Stage I-II HR: 0.76 (0.68-0.86); Stage III-IV HR: 1.08 (0.82-1.43) |
Braghiroli et al[141], 2015 | Single-arm phase II. n = 20 | Locally advanced or metastatic. 2nd line treatment. Single center. Brazilian | Paclitaxel (80 mg/m2 D1, 8, 15 every 28 d) + metfomin 1750 mg/d | DCR at 8 wk 31, 6% |
Pancreatic neuroendocrine tumor | ||||
Pusceddu et al[153], 2018 | Retrospective cohort. n = 445 | Locally advanced or metastatic. Multicentric. Italian | No DM2 vs DM2. Metformin user vs nonuser | HR: 0.45 (0.32-0.62). HR: 0.49 (0.34-0.69) |
Hepatocellular carcinoma | ||||
Chen et al[163], 2011 | Retrospective cohort. n = 53 | DM2. Early-stage HCC. RFA treated. Single center. Taiwanese | Metformin user vs nonuser | HR: 0.24 (0.07-0.90) |
Ma et al[164], 2016 | Meta-analysis. 11 cohort studies. n = 3452 | Studies that investigated metformin exposition. HCC patients | Metformin user vs nonuser | HR: 0.59 (0.42-0.83) |
Intrahepatic cholangiocarcinoma | ||||
Yang et al[169], 2016 | Retrospective cohort. n = 250 | DM2. Newly diagnosed ICC. United States single center | Metformin user vs nonuser | HR: 0.80 (0.60-1.20) |
- Citation: Cunha Júnior AD, Bragagnoli AC, Costa FO, Carvalheira JBC. Repurposing metformin for the treatment of gastrointestinal cancer. World J Gastroenterol 2021; 27(17): 1883-1904
- URL: https://www.wjgnet.com/1007-9327/full/v27/i17/1883.htm
- DOI: https://dx.doi.org/10.3748/wjg.v27.i17.1883