Clinical Effect Of Metformin Combined With Chemotherapy For Small Cell Lung Cancer Complicated With Diabetes Mellitus

BackgroundThe incidence of cancer and diabetes in the world is increasing year by year.According to the latest cancer report in China,the incidence of lung cancer ranks first among all tumors.It is estimated that there are 787000 new cases of lung cancer in China in 2015.The incidence was 57.26/100000.631000 cases died of lung cancer,the mortality rate was 45.87/100000.More and more clinical evidence suggests that there may be risk factors affecting tumor development and progression in diabetic patients.It is reported that type 2 diabetes mellitus is associated with increased incidence of breast cancer,gastrointestinal tumors,pancreatic cancer,renal cell carcinoma,bladder cancer and thyroid cancer,as well as poor tumor-related survival and prognosis.Although the treatment of lung cancer has developed rapidly in recent years,especially the research and development of targeted therapeutic drugs has achieved clinical efficacy,but on the whole,the prognosis of lung cancer is not optimistic.Currently,the research on targeted drugs for small cell lung cancer(SCLC)is not completely mature,and its main treatment methods are still chemotherapy and radiotherapy,lacking of new therapeutic drugs and methods to improve the prognosis and survival of such patients.Metformin is a first-line treatment for type 2 diabetes due to its advantages of good tolerance,high safety and good efficacy.Several studies have demonstrated its anti-tumor effects in a variety of cancers,including lung cancer.Although the specific mechanism is not clear,current researchers have studied the anti-tumor mechanism in a variety of tumor cells and tissues,including mTOR pathway,AMPK pathway,MAPK pathway and leptin.Meanwhile,the anti-tumor effect of metformin on lung cancer has also been widely studied.Xu et al.reported that metformin can improve the prognosis of SCLC patients with diabetes.Lin et al.proved that metformin can improve the survival rate of patients with stage IV non-small cell lung cancer(NSCLC)complicated with diabetes.But Mazzone et al.found that patients with diabetes treated with metformin may have a worse prognosis if they develop lung cancer.At present,there are relatively few clinical studies on metformin in SCLC,and we hope to carry out clinical studies to observe its specific impact on the prognosis and survival of SCLC.Objectives:This study screened,collected,and recorded the clinical features,prognosis,and chemotherapy-related adverse reactions in SCLC patients with type 2 diabetes,and explored the effects of metformin combined with chemotherapy on the clinical efficacy and prognosis of patients,providing clinical data for metformin as a potential anticancer drug.Methods:A retrospective study of 51 patients with pathologically confirmed SCLC and type2 diabetes mellitus treated in the Department of Oncology of the First Affiliated Hospital of Zhengzhou University was divided into observation group and control group according to whether metformin was used during chemotherapy.A total of 26patients in the observation group were treated with chemotherapy combined with metformin,and 25 patients in the control group were treated with chemotherapy and other hypoglycemic agents other than metformin.The basic clinical characteristics such as age,gender,tumor stage,smoking history,history of radiotherapy,other medical history,PS score,adverse effects like bone marrow suppression,hepato-renal toxicity,gastrointestinal upset were observed and recorded.The recent curative effect of patients was evaluated according to the RECIST(version 1.1)criteria.The performance status(PS)of the patients was assessed by ECOG scale.The Common Toxicity Criteria for Adverse Events(CTCAE)version 5.0 was used to determine the toxicity profile of the patients during chemotherapy.The basic clinical features and adverse reactions during chemotherapy were compared byχ~2 test.PFS and OS were compared between the two groups by Kaplan-Meier method,and the factors that might affect the prognosis were analyzed by Cox proportional hazards regression model.The above statistical analyses were used to evaluate the effect of metformin on the prognosis and adverse effects of SCLC patients with type 2 diabetes.Results:There was no significant difference in the distribution of basic clinical parameters such as sex,age,smoking history,history of radiotherapy,other medical history,PS score and tumor stage between the observation group and the control group(P>0.05).There was no significant difference between the two groups in bone marrow suppression,hepato-renal toxicity,gastrointestinal upset and other common adverse reactions of chemotherapy(P>0.05).The median PFS of the observation group(9.03months)was significantly higher than the control group(6.23 months)and the difference was statistically significant(P<0.05).The median OS of the observation group was 19.2 months and the median OS of the control group was 13.5 months and the difference was statistically significant(P<0.05).Cox regression analysis showed that metformin,PS score,history of radiotherapy and stage were independent prognostic factors of OS,metformin and PS score were independent prognostic factors of PFS.Conclusion:Metformin combined with chemotherapy can significantly improve PFS and OS in patients with SCLC and type 2 diabetes,and metformin is one of the prognostic factors in patients with SCLC and type 2 diabetes.