Metformin use improves the survival of diabetic combined small-cell lung cancer patients

Kong, Fanming; Gao, Fangfang; Liu, Honggen; Chen, Liwei; Ruan, Zheng; Yu, Jianchun; Li, Xiaojiang; Liu, Geli; Jia, Yulin

doi:10.1007/s13277-015-3549-1

Cited by 31 publications

(27 citation statements)

References 34 publications

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“…All the included studies were reported in English. Of the 10 articles [17–19, 21–27], 1 described case-control design and 5 described cohort design involved Western region, and 4 described cohort design involved Asian region. Moreover, there were two publications focusing on SCLC, five on NSCLC, one on mixed cancers including SCLC and NSCLC, and two with unavailable information concerned.…”

Section: Resultsmentioning

confidence: 99%

Metformin therapy associated with survival benefit in lung cancer patients with diabetes

Wan

Chen

et al. 2016

Oncotarget

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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.

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Section: Resultsmentioning

confidence: 99%

Metformin therapy associated with survival benefit in lung cancer patients with diabetes

Wan

Chen

et al. 2016

Oncotarget

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“…Some, but not all [8] have reported improvements in progressionfree survival [9] and disease-free survival [10,11] but these investigations were limited by small sample sizes [8][9][10][11], drug exposure determined at limited numbers of time-points [8][9][10][11] and a lack of adjustment for important baseline patient characteristics [9]. Other studies have investigated metformin use and overall survival [12][13][14], but these results could reflect mortality from non-cancer causes.…”

Section: Introductionmentioning

confidence: 99%

Metformin use and survival from lung cancer: A population-based cohort study

et al. 2016

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word count: 222 Manuscript word count: 1,472Number of tables and figures: 2 Abbreviations: BMI, body mass index; CIs, confidence intervals; CPRD, Clinical Practice Research Datalink; DDD, daily defined dose; GP, general practitioner; HR, hazard ratio; NCDR, National cancer Data Repository; ONS, Office of National Statistics; UK, United Kingdom; WHO, World Health Organisation. AbstractPreclinical evidence suggests that metformin, a widely prescribed anti-diabetic drug, may inhibit lung cancer progression. We investigated whether metformin use was associated with decreased risk of cancer-specific mortality in lung cancer patients. This study included newly diagnosed lung cancer patients (identified from English National Cancer Data Repository, 1998-2009) with type 2 diabetes (based on UK Clinical Practice Research Datalink prescriptions and diagnosis records). Lung cancer deaths occurring up to 2012 were identified using Office of National Statistics mortality data and the association between metformin use (before and after diagnosis) and risk of lung cancer-specific mortality was calculated using Cox regression models. In analysis of 533 patients, we found a weak non-significant reduction in lung cancer-specific mortality with metformin use after diagnosis (adjusted HR, 0.86; 95% CI, 0.68-1.09). No association was evident for metformin use before diagnosis and cancer-specific mortality in analysis of 1,350 patients (adjusted HR, 0.97; 95% CI, 0.86, 1.11). Associations were similar by duration of use. In addition, after adjustment for potential confounders, there was little evidence of an association between the use of other anti-diabetic medications (either before or after diagnosis) and lung cancer-specific mortality; including sulfonylureas, insulin or other anti-diabetic medications (such as thiazolidinediones). Overall, the results from this population-based study provide little evidence of a protective association between metformin use and cancer mortality in lung cancer patients.

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“…A close examination of these studies revealed that these studies differed by timing of metformin exposure, population characteristics (cancer stage and histology), reference group, and adjustment for confounders. A study on small cell lung cancer reported improved survival 30 , but the time window of metformin use was unclear. In a study of 750 Stage IV NSCLC patients based on the SEER-Medicare data, pre-diagnostic metformin use was associated with significantly improved overall survival, after adjustment for tumor characteristics and chemotherapy 28 .…”

Section: Discussionmentioning

confidence: 99%

Metformin use and survival after non‐small cell lung cancer: A cohort study in the US Military health system

Lin

Gill

Zahm

et al. 2017

Intl Journal of Cancer

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Research suggests that metformin may be associated with improved survival in cancer patients with type II diabetes. This study assessed whether metformin use after non-small cell lung cancer (NSCLC) diagnosis is associated with overall survival among type II diabetic patients with NSCLC in the U.S. military health system (MHS). The study included 636 diabetic patients with histologically confirmed NSCLC diagnosed between 2002 and 2007, identified from the linked database from the Department of Defense’s Central Cancer Registry (CCR) and the Military Health System Data Repository (MDR). Time-dependent multivariate Cox proportional hazards models were used to assess the association between metformin use and overall survival during follow up. Among the 636 patients, 411 died during the follow up. The median follow up time was 14.6 months. Increased post-diagnosis cumulative use (per one-year of use) conferred a significant reduction in mortality (adjusted hazard ratio (HR)=0.76; 95% CI=0.65 to 0.88). Further analysis by duration of use revealed that compared to non-users, the lowest risk reduction occurred among patients with the longest duration of use (i.e. use for more than 2 years) (HR=0.19; 95% CI=0.09 to 0.40). Finally, the reduced mortality was particularly observed only among patients who also used metformin before lung cancer diagnosis and among patients at early stage of diagnosis. Prolonged duration of metformin use in the study population was associated with improved survival, especially among early stage patients. Future research with a larger number of patients is warranted.

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Metformin use improves the survival of diabetic combined small-cell lung cancer patients

Cited by 31 publications

References 34 publications

Metformin therapy associated with survival benefit in lung cancer patients with diabetes

Metformin therapy associated with survival benefit in lung cancer patients with diabetes

Metformin use and survival from lung cancer: A population-based cohort study

Metformin use and survival after non‐small cell lung cancer: A cohort study in the US Military health system

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