Prognostic influence of metformin as first‐line chemotherapy for advanced nonsmall cell lung cancer in patients with type 2 diabetes

Tan, Bing; Yao, Wenxiu; Ge, Jun; Peng, Xingchen; Du, Xiaobo; Zhang, Ru; Yao, Bin; Xie, Ke; Li, Longhao; Hang, Dong; Gao, Feng; Zhao, Feng; Hou, Jianmei; Su, Jingmei; Liu, Jiyan

doi:10.1002/cncr.26151

Cited by 153 publications

(141 citation statements)

References 55 publications

(73 reference statements)

Supporting

Mentioning

124

Contrasting

Unclassified

Order By: Relevance

“…This is an example of an effect modification (although in this example the authors did not formally test for an interaction). Furthermore, two recently published studies have found similar beneficial effects of metformin among patients with colorectal cancer and diabetes [72], and among patients with advanced non-small-cell lung cancer undergoing first-line chemotherapy [73].…”

Section: Effects Of Glucose-lowering Treatments On Cancer Treatmentsmentioning

confidence: 79%

Diabetes and cancer (2): evaluating the impact of diabetes on mortality in patients with cancer

et al. 2012

View full text Add to dashboard Cite

In this paper we address methodological aspects of aetiological importance in the link between diabetes and mortality in patients with cancer. We identified nine key points on the cancer pathway at which confounding may arise-cancer screening use, stage at diagnosis, cancer treatment selection, cancer treatment complications and failures, peri-treatment mortality, competing risks for long-term mortality, effects of type 2 diabetes on anti-cancer therapies, effects of glucoselowering treatments on cancer outcome and differences in tumour biology. Two types of mortality studies were identified: (1) inception cohort studies that evaluate the effect of baseline diabetes on cancer-related mortality in general populations, and (2) cohorts of patients with a cancer diagnosis and preexisting type 2 diabetes. We demonstrate, with multiple examples from the literature, that pre-existing diabetes affects presentation, cancer treatment, and outcome of several common cancer types, often to varying extents. Diabetes is associated with increased all-cause mortality in cancer patients, but the evidence that it influences cancer-specific mortality is inconsistent. In the absence of data that address the potential biases and confounders outlined in the above framework, we caution against the reporting of cancer-related mortality as a main endpoint in analyses determining the impact of diabetes and glucose-lowering medications on risk of cancer.

show abstract

Section: Effects Of Glucose-lowering Treatments On Cancer Treatmentsmentioning

confidence: 79%

Diabetes and cancer (2): evaluating the impact of diabetes on mortality in patients with cancer

et al. 2012

View full text Add to dashboard Cite

show abstract

“…In a retrospective casecontrol study, Mazzone and colleagues (31) found that metformin was associated with a more aggressive lung cancer phenotype and worse prognosis. Conversely, two observational studies, a small Chinese study with patients with lung cancer and a larger UK study that included many cancer types, showed that metformin was associated with improved survival in patients with lung cancer (17,18). A major limitation of these studies is the lack of adjustment for baseline patient characteristics that might account for metformin use.…”

Section: Discussionmentioning

confidence: 99%

“…One small retrospective study from China showed that patients with diabetes with lung cancer treated with metformin had improved overall and progression-free survival (18). However, the effect of metformin on lung cancer outcomes has not been validated in larger samples.…”

Section: At a Glance Commentarymentioning

confidence: 99%

Survival of Patients with Stage IV Lung Cancer with Diabetes Treated with Metformin

Lin

Gallagher

Sigel

et al. 2015

Am J Respir Crit Care Med

121

106

View full text Add to dashboard Cite

Rationale: Prior studies have shown an anticancer effect of metformin in patients with breast and colorectal cancer. It is unclear, however, whether metformin has a mortality benefit in lung cancer.Objectives: To compare overall survival of patients with diabetes with stage IV non-small cell lung cancer (NSCLC) taking metformin versus those not on metformin.Methods: Using data from the Surveillance, Epidemiology, and End Results registry linked to Medicare claims, we identified 750 patients with diabetes 65-80 years of age diagnosed with stage IV NSCLC between 2007 and 2009. We used propensity score methods to assess the association of metformin use with overall survival while controlling for potential confounders.Measurements and Main Results: Overall, 61% of patients were on metformin at the time of lung cancer diagnosis. Median survival in the metformin group was 5 months, compared with 3 months in patients not treated with metformin (P , 0.001). Propensity score analyses showed that metformin use was associated with a statistically significant improvement in survival (hazard ratio, 0.80; 95% confidence interval, 0.71-0.89), after controlling for sociodemographics, diabetes severity, other diabetes medications, cancer characteristics, and treatment.Conclusions: Metformin is associated with improved survival among patients with diabetes with stage IV NSCLC, suggesting a potential anticancer effect. Further research should evaluate plausible biologic mechanisms and test the effect of metformin in prospective clinical trials.

show abstract

“…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

View full text Add to dashboard Cite

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.

show abstract

Prognostic influence of metformin as first‐line chemotherapy for advanced nonsmall cell lung cancer in patients with type 2 diabetes

Cited by 153 publications

References 55 publications

Diabetes and cancer (2): evaluating the impact of diabetes on mortality in patients with cancer

Diabetes and cancer (2): evaluating the impact of diabetes on mortality in patients with cancer

Survival of Patients with Stage IV Lung Cancer with Diabetes Treated with Metformin

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

Contact Info

Product

Resources

About