Abstract
Aims Metformin is an oral antidiabetic agent that has been widely prescribed for the treatment of type II diabetes. In recent years, anticancer properties of metformin have been revealed for numerous human malignancies. However, there are few indications available regarding the feasibility and safety of these studies in an advanced extrahepatic cholangiocarcinoma (EHCC) population. This study is aimed at evaluating the feasibility, safety, and value of metformin use and survival in patients with advanced EHCC. Methods All patients with advanced EHCC observed at Fuyang People's Hospital between January 2015 and November 2020 were included in the study. Case data, clinical information, and imaging results were abstracted from the self-administered questionnaire and electronic medical record. All patients were divided into study subjects and control subjects, and the study subjects were given metformin, 0.5 g, three times a day, while control subjects were without metformin. The metformin use and survival time of the subjects were asked by telephone, out-patient, or door-to-door visit, after they left the hospital. Results One hundred and thirty-three study cases and 589 controls were included in the analysis. This study showed that metformin use cannot improve the overall survival rate of patients with advanced EHCC ([95% CI]: -17.05-0.375, t = −1.889, P value = 0.061), but the survival time of patients with drainage treatment from control group (n = 496) was significantly shorter than that of patients with drainage treatment from the study group (n = 113), and the difference was statistically significant (z = −2.230, P value = 0.026). There were significant differences between metformin used before or after the diagnosis of advanced EHCC (OR[95% CI], 3.432[2.617-4.502]; P value = 0.001) in survival time. And there was significant difference between the duration of metformin use and survival prognosis (OR[95% CI], 2.967[1.383-6.368]; P = 0.005). Conclusion Metformin can improve the survival of advanced EHCC patients who underwent drainage treatment, especially for metformin use after diagnosis of advanced EHCC and long duration of metformin.
Highlights
Cholangiocarcinoma (CCA) is categorized as an distal cholangiocarcinoma, perihilar, and intrahepatic [1]
This study showed that the number of patients who actively withdrew from using metformin due to intolerance was only 7 (5.26%), while survival time was shorter (Table 5)
This study showed that metformin use cannot improve the overall survival rate of patients with advanced extrahepatic cholangiocarcinoma (EHCC) ([95% confidence intervals (95% CI)]: -17.05-0.375; t = −1:889, P value = 0.061, Figure 1), but the survival time of patients with drainage treatment using metformin was significantly longer than that of patients without metformin (z = −2:230, P value = 0.026)
Summary
Cholangiocarcinoma (CCA) is categorized as an distal cholangiocarcinoma, perihilar, and intrahepatic [1]. Metformin is an oral antidiabetic agent that has been widespread prescribed for treatment of type II diabetes [9, 10]. This drug lowers hyperglycemia through the inhibition of hepatic glucose production. Cancer cells preferentially metabolize glucose to lactate, even in aerobic conditions Such metabolic alterations promote the growth and invasion of tumor cells and support their chemoresistance [11]. The effects of metformin on survival and prognosis of patients with advanced EHCC were assessed
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