Title: Impact of Metformin Use on Survival in Non-Small Cell Lung Cancer Treated With Definitive Radiation Therapy
Abstract: Metformin use with radiation therapy (RT) has exhibited a positive effect on either survival or pathologic complete response in ovarian, rectal, prostate, breast, esophageal and laryngeal cancers. However metformin use was found to have no effect on survival in patients with oropharyngeal cancer treated with RT, nor on patients with pancreatic, colorectal or prostate cancers treated surgically and/or medically. In vitro, metformin has demonstrated general anti-cancer activity via the AMP-kinase and mTOR pathways. It has also been found to inhibit non-small cell lung cancer (NSCLC) cell and tumor growth in vitro and to sensitize them to ionizing radiation. In this retrospective analysis we investigated survival outcomes in diabetic patients with NSCLC treated with definitive RT and previously on concurrent metformin. This single-institution, institutional review board-approved, retrospective cohort study included 166 patients with NSCLC who were treated definitively with platinum-based doublet chemotherapy and thoracic RT to 60 Gy between 1999 and 2013. Of 40 patients who had type II diabetes (DM), 20 were on metformin (DM+met), and 20 were not on metformin (DM–met). Univariate and multivariate analyses compared overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS) and locoregional recurrence-free survival (LRRFS) between DM+met vs DM–met as well as DM+met vs non-DM patients. Mean follow-up for all patients was 23.2 months. Log-rank test found no significant difference between DM+met and DM–met in OS (18.5 vs 25.0 mo, p = 0.180), PFS (12.3 vs 14.5 mo, p = 0.378), LRRFS (14.7 vs 21.1 mo, p = 0.691), and DMFS (15.0 vs 16.5 mo, p = 0.116). In DM+met patients versus non-DM patients, no significant difference was observed in OS (18.5 vs 23.6 mo, p = 0.228), PFS (12.3 v. 23.6, p = 0.260), LRRFS (14.7 vs 20.6, p = 0.784), and DMFS (15.0 vs 19.5 mo, p = 0.497). The cohorts were similar except for BMI (30.7 vs 26.2, p = 0.010) and the presence of hypertension (80% vs 51%, p = 0.026), which were both significantly greater in DM+met group vs non-DM cohort. Identified negative prognostic factors on univariate analysis included squamous cell histology, lower performance status, higher T stage, and non-white ethnicity. No statistically significant differences in survival or patterns of failure were found between the three cohorts in this small set of patients. Though it is possible that metformin use may in fact have no effect on survival in NSCLC patients treated with definitive RT, larger-scale retrospective and prospective studies are implicated for clarification.
Publication Year: 2014
Publication Date: 2014-09-01
Language: en
Type: article
Indexed In: ['crossref']
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Cited By Count: 1
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