The Study For Metformin On The Chemotherapy Effect And Adverse Reactions In Patients With Lung Cancer

Objective: To systematically evaluate the impact of metformin adjunct with conventional anti-tumor drugs on the survival outcomes of patients with lung cancer,and the efficacy of metformin combined with standard first-line therapy on objective response and survival in patients with advanced non-small cell lung cancer(NSCLC).Cohort study was conducted to analyze the the effect of metformin on platinum-based chemotherapy in patients with NSCLC and type 2 diabetes mellitus.Methods: 1.In the first part,an electronic literature search including Embase,Pub Med,Cochrane Library and Web of Science was performed to obtain relevant studies on the impact of metformin adjunct with conventional anti-tumor drugs on the survival outcomes of patients with lung cancer.Overall survival(OS)and progression-free survival(PFS)were statistically analyzed using the Review Manager 5.3 software.2.In the second part,we searched databases,including Embase,Pub Med,Cochrane Library,Web of Science,Clinical Trials,CBM,CNKI,WANFANG and VIP database to obtain clinical studies on the effect of metformin combined with standard first-Line therapy for patients with advanced NSCLC.The end points included OS,PFS and objective response rate(ORR).Review Manager5.3 software was used to perform the Meta-analysis.3.In the third part,we retrospectively collected the clinical and data of 157 patients with NSCLC and type2 diabetes who received platinum-based first-line chemotherapy in the First Affiliated Hospital of China Medical University from 2012 to 2019.They were divided into two groups according to whether metformin was used during chemotherapy.A total of 85 patients in the observation group were treated with metformin,and 72 patients in the control group were treated with hypoglycemic drugs other than metformin.SPSS 25.0 statistical software was used to process the data,and the PFS,OS,ORR,disease control rate(DCR)and adverse reactions during chemotherapy of the two groups was compared.Besides,Cox regression analysis was performed on factors that may affect the prognosis.Results: 1.Sixteen studies consisting 4087 patients were included in the Meta-analysis.Compared to standard antineoplastic agents alone,the antineoplastic agents combined with metformin significantly improved OS(HR=0.73,95%CI:0.66-0.81)and PFS(HR=0.72,95%CI: 0.59-0.88)in patients with lung cancer.2.A total of fourteen studies were included in this study,totaling 4910 participants with advanced NSCLC undergoing standard first-line treatment.According to Meta-analysis,patients treated with metformin had significantly longer OS(HR=0.77,95%CI: 0.69-0.86)and PFS(HR=0.83,95%CI: 0.72-0.96)than patients treated without metformin,such association was also presented in ORR(RR=1.19,95%CI: 1.04-1.35),and the difference was statistically significant(P<0.05).3.The median PFS in the observation group was 12.0 months(95%CI: 7.0-16.3).The median PFS in the control group was 11.0 months(95%CI: 8.2-13.8).There was with no significant difference(P>0.05).The median OS was significantly longer in the observation group(29.0 months,95% CI: 14.6-43.5)than in the control group(21.0 months,95% CI: 18.2-23.9);and multivariate analysis showed that metformin was an independent prognostic factors of OS(HR=0.67,95% CI: 0.44-0.98,P=0.042).There were no significant difference between the two group in ORR and DCR(46.0% vs 37.0%,96.0% vs 89.1%).The incidences of gastrointestinal reaction,myelosuppression,hepatorenal toxicity and grade 3/4 adverse reactions in the observation group were 60.00%,50.59%,10.59% and 28.24% respectively,and there was no significant difference compared with 61.11%,52.78%,9.72% and27.78% in the control group(P>0.05).Conclusions: 1.Metformin combined with antineoplastic agents may improve OS and PFS of patients with lung cancer.2.The use of metformin is positive for the prognosis of patients with advanced lung cancer receiving standard first-line therapy,it may improve ORR,PFS and OS.3.Platinum-based chemotherapy combined with metformin can significantly improve OS in patients with NSCLC and type 2diabetes,and does not increase the incidence of chemotherapy-related adverse reactions.In addition,metformin is an independent prognostic factor for OS in patients with NSCLC concurrent type 2 diabetes receiving platinum-based first-line chemotherapy.