Robert A Medairos1, James Clark1, Simon Holoubek1, John C Kubasiak2, Ravi Pithadia3, Fatima Hamid4, Gary W Chmielewski1, William H Warren1, Sanjib Basu5, Jeffrey A Borgia6, Michael J Liptay1, Christopher W Seder7. 1. Department of Cardiovascular and Thoracic Surgery, Rush University Medical Center, Chicago, Ill. 2. Department of General Surgery, Rush University Medical Center, Chicago, Ill. 3. Department of Biochemistry, Rush University Medical Center, Chicago, Ill. 4. Department of Pathology, Rush University Medical Center, Chicago, Ill. 5. Department of Preventative Medicine, Rush University Medical Center, Chicago, Ill. 6. Department of Biochemistry, Rush University Medical Center, Chicago, Ill; Department of Pathology, Rush University Medical Center, Chicago, Ill. 7. Department of Cardiovascular and Thoracic Surgery, Rush University Medical Center, Chicago, Ill. Electronic address: Christopher_W_Seder@rush.edu.
Abstract
OBJECTIVE: There are little clinical data assessing the antineoplastic effect of metformin in patients with non-small cell lung cancer. We hypothesized that in diabetic patients undergoing pulmonary resection for early-stage non-small cell lung cancer, metformin exposure is associated with improved survival. METHODS: An institutional database was used to identify patients with stage I or II non-small cell lung cancer who underwent pulmonary resection between 2004 and 2013. Patients were divided into 3 cohorts: type II diabetic patients with metformin exposure (cohort A, n = 81), type II diabetic patients without metformin exposure (cohort B, n = 57), and nondiabetic individuals (cohort C, n = 77). Univariate, multivariate, and propensity-matched analyses were performed to assess progression-free and overall survivals between groups. RESULTS: A total of 215 patients with stage I and II non-small cell lung cancer treated with surgical resection were identified for analysis with a median follow-up of 19.5 months. Patients in cohort A had lower T- and N-stage tumors than those in cohorts B or C. However, on multivariate analysis adjusting for age, gender, and T and N stage, progression-free survival was greater for cohort A than cohort B (hazard ratio [HR], 0.410; 95% confidence interval, 0.199-0.874; P = .022) or cohort C (HR, 0.415; 95% confidence interval, 0.201-0.887; P = .017). Likewise, when propensity-matched analyses were performed, cohort A demonstrated a trend toward improved progression-free survival compared with cohort B (P = .057; HR, 0.44; c-statistic = 0.832) and improved progression-free survival compared with cohort C (P = .02; HR, 0.41; c-statistic = 0.843). No differences were observed in overall survival. CONCLUSIONS: Metformin exposure in diabetic patients with early-stage non-small cell lung cancer may be associated with improved progression-free survival, but no effect was seen on overall survival. Further studies are warranted to evaluate if there is a therapeutic role for metformin in the treatment of non-small cell lung cancer.
OBJECTIVE: There are little clinical data assessing the antineoplastic effect of metformin in patients with non-small cell lung cancer. We hypothesized that in diabeticpatients undergoing pulmonary resection for early-stage non-small cell lung cancer, metformin exposure is associated with improved survival. METHODS: An institutional database was used to identify patients with stage I or II non-small cell lung cancer who underwent pulmonary resection between 2004 and 2013. Patients were divided into 3 cohorts: type II diabeticpatients with metformin exposure (cohort A, n = 81), type II diabeticpatients without metformin exposure (cohort B, n = 57), and nondiabetic individuals (cohort C, n = 77). Univariate, multivariate, and propensity-matched analyses were performed to assess progression-free and overall survivals between groups. RESULTS: A total of 215 patients with stage I and II non-small cell lung cancer treated with surgical resection were identified for analysis with a median follow-up of 19.5 months. Patients in cohort A had lower T- and N-stage tumors than those in cohorts B or C. However, on multivariate analysis adjusting for age, gender, and T and N stage, progression-free survival was greater for cohort A than cohort B (hazard ratio [HR], 0.410; 95% confidence interval, 0.199-0.874; P = .022) or cohort C (HR, 0.415; 95% confidence interval, 0.201-0.887; P = .017). Likewise, when propensity-matched analyses were performed, cohort A demonstrated a trend toward improved progression-free survival compared with cohort B (P = .057; HR, 0.44; c-statistic = 0.832) and improved progression-free survival compared with cohort C (P = .02; HR, 0.41; c-statistic = 0.843). No differences were observed in overall survival. CONCLUSIONS:Metformin exposure in diabeticpatients with early-stage non-small cell lung cancer may be associated with improved progression-free survival, but no effect was seen on overall survival. Further studies are warranted to evaluate if there is a therapeutic role for metformin in the treatment of non-small cell lung cancer.
Authors: Suzan Brancher; Nathalie C Støer; Elisabete Weiderpass; Ronald A M Damhuis; Tom B Johannesen; Edoardo Botteri; Trond-Eirik Strand Journal: Br J Cancer Date: 2020-12-02 Impact factor: 7.640