Absence of antitumor effects of metformin in sorafenib-treated patients with hepatocellular carcinoma recurrence after hepatic resection and liver transplantation

BACKGROUNDS/AIMS: Hepatocellular carcinoma (HCC) recurrence following hepatic resection (HR) and liver transplantation (LT) remains a great concern. We assessed the antitumor effects of metformin in patients treated with sorafenib for HCC recurrence after HR or LT. METHODS: The two clinical retrospective studies involved metformin therapy of 304 HR patients and 74 LT recipients who were treated with sorafenib. RESULTS: In the study involving patients who had undergone HR, death occurred in 245 of the 304 patients (80.6%) during a median follow-up of 10.2 months after sorafenib administration. The metformin HR group (group 1; n=40) showed no prognostic difference in progression-free and overall survival rates compared with the all-HR control group (group 3; n=241) and propensity score-matched HR control group (group 4; n=80). In the clinical study of recipients exposed to LT, death occurred in 62 of the 74 patients (83.8%) during a median follow-up of 13.6 months (range: 3–76 months) after sorafenib administration. The metformin LT group (group 5; n=14) showed no prognostic difference in progression-free and overall survival rates compared with the all-LT control group (group 7; n=43) and propensity score-matched LT control group (group 8; n=28). CONCLUSIONS: Our clinical studies demonstrated absence of synergistic antitumor effects of metformin. Further high-volume studies are necessary to assess the role of metformin in patients treated with sorafenib for advanced HCC.