Abstract
The purpose of this study is to summarize the currently available evidence regarding the concerned issue by performing a comprehensive meta-analysis. Relevant publications reporting the association of metformin use with survival of lung cancer patients with diabetes were electronically searched to identify eligible studies. The meta-analysis was performed with hazard ratios (HRs) and 95% confidence intervals (95% CIs) as effect measures for disease-free survival(DFS) and overall survival(OS) estimates. A total of 17 individual studies from 10 publications were included in the meta-analysis. Overall, the results revealed a significant association of metformin use with a better survival of lung cancer patients with diabetes(for DFS: HR = 0.65, 95%CI = 0.52-0.83; for OS: HR = 0.78, 95%CI = 0.64-0.93). The subgroup analyses showed similar association in Asian region(for DFS:HR = 0.69, 95%CI = 0.59-0.80; for OS: HR = 0.55, 95%CI = 0.46-0.67) but not in Western region. Such association was also presented in small cell lung cancer (for DFS: HR = 0.54, 95%CI = 0.38-0.77; for OS: HR = 0.52, 95%CI = 0.39-0.69) and in non-small cell lung cancer(for DFS: HR = 0.70, 95%CI = 0.51-0.96; for OS: HR = 0.75, 95%CI = 0.58-0.97). Analyses stratified by treatment strategy showed a reduction in the risk of cancer-related mortality in patients receiving chemotherapy(for DFS: HR = 0.71, 95%CI = 0.64-0.83; for OS: HR = 0.58, 95%CI = 0.47-0.71) but not in patients receiving chemoradiotherapy. The meta-analysis demonstrated that metformin use was significantly associated with a favorable survival outcome of lung cancer patients with diabetes.
Highlights
According to the epidemiologic and clinical studies, approximately 8% to 18% of individuals survived with a diagnosis of cancer accompanying with diabetes, probably due to the shared risk factors of the diseases, such as greater body mass index, smoking, and the lack of exercise and their growing global prevalence [1, 2]
The exact mechanism was not fully understood as yet, some in vitro www.impactjournals.com/oncotarget and in vivo studies have demonstrated with the increasing attention attached to the metformin-mediated therapy in lung cancer, that metformin may exert the antitumor activity through indirect effects and direct effects on the inhibition of cancer cell proliferation, colony formation, migration, and invasion, and the induction of cell cycle arrest and apoptosis mediated by the ATM/LKB1/AMPK axis and mammalian target of rapamycin-signaling pathway [12,13,14,15,16]
Increasing evidence has strengthened the effects of metformin on prevention and treatment of lung cancer in recent years though the exact molecular mechanism for the anti-cancer role of metformin has not been fully unveiled to date
Summary
According to the epidemiologic and clinical studies, approximately 8% to 18% of individuals survived with a diagnosis of cancer accompanying with diabetes, probably due to the shared risk factors of the diseases, such as greater body mass index, smoking, and the lack of exercise and their growing global prevalence [1, 2]. A number of epidemiological studies have investigated the prognostic significance of metformin use in lung cancer patients with diabetes, but obtained inconsistent results. Tan et al reported that metformin may improve chemotherapy outcomes and survival for advanced non-small cell lung cancer (NSCLC) patients with type 2 diabetes [17]. Xu et al observed a beneficial survival of metformin use in small cell lung cancer(SCLC) patients with diabetes [18]. In an effort to bring more clarity to this issue, a meta-analysis of currently available relevant observational studies was carried out to systematically reassess the effect of metformin use on the survival outcome of lung cancer patients with diabetes
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