The Impact of Diabetes Mellitus and Metformin Treatment on Survival of Patients with Advanced Pancreatic Cancer Undergoing Chemotherapy
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Purpose A causal relationship between diabetes mellitus (DM) and pancreatic cancer is well estab- lished. However, in patients with advanced pancreatic cancer (APC) who receive palliative chemotherapy, the impact of DM on the prognosis of APC is unclear. Materials and Methods We retrospectively enrolled APC patients who received palliative chemotherapy between 2003 and 2010. The patients were stratified according to the status of DM, in accordance with 2010 DM criteria (American Heart Association/American Diabetes Association). DM at least 2 years’ duration prior to diagnosis of APC was defined as remote-onset DM (vs. recent-onset). Results Of the 349 APC patients, 183 (52.4%) had DM. Among the patients with DM, 160 patients had DM at the time of diagnosis of APC (remote-onset, 87; recent-onset, 73) and the remaining 23 patients developed DM during treatment of APC. Ultimately, 73.2% of patients (134/183) with DM received antidiabetic medication, including metformin (56 patients, 41.8%), sulfonylurea (62, 45.5%), and insulin (43, 32.1%). In multivariate analysis, cancer extent (hazard ratio [HR], 1.792; 95% confidence interval [CI], 1.313 to 2.445; p < 0.001) showed association with decreased overall survival (OS), whereas a diagnosis of DM (HR, 0.788; 95% CI, 0.615 to 1.009; p=0.059) conferred positive tendency on the OS. Metformin treatment itself conferred better OS in comparison within DM patients (HR 0.693; 95% CI, 0.492 to 0.977; p=0.036) and even in all APC patients (adjusted HR, 0.697; 95% CI, 0.491 to 1.990; p=0.044). Conclusion For APC patients receiving palliative chemotherapy, metformin treatment is associated with longer OS. Patients with DM tend to survive longer than those without DM.
Abstract
Purpose A causal relationship between diabetes mellitus (DM) and pancreatic cancer is well estab- lished. However, in patients with advanced pancreatic cancer (APC) who receive palliative chemotherapy, the impact of DM on the prognosis of APC is unclear. Materials and Methods We retrospectively enrolled APC patients who received palliative chemotherapy between 2003 and 2010. The patients were stratified according to the status of DM, in accordance with 2010 DM criteria (American Heart Association/American Diabetes Association). DM at least 2 years’ duration prior to diagnosis of APC was defined as remote-onset DM (vs. recent-onset). Results Of the 349 APC patients, 183 (52.4%) had DM. Among the patients with DM, 160 patients had DM at the time of diagnosis of APC (remote-onset, 87; recent-onset, 73) and the remaining 23 patients developed DM during treatment of APC. Ultimately, 73.2% of patients (134/183) with DM received antidiabetic medication, including metformin (56 patients, 41.8%), sulfonylurea (62, 45.5%), and insulin (43, 32.1%). In multivariate analysis, cancer extent (hazard ratio [HR], 1.792; 95% confidence interval [CI], 1.313 to 2.445; p < 0.001) showed association with decreased overall survival (OS), whereas a diagnosis of DM (HR, 0.788; 95% CI, 0.615 to 1.009; p=0.059) conferred positive tendency on the OS. Metformin treatment itself conferred better OS in comparison within DM patients (HR 0.693; 95% CI, 0.492 to 0.977; p=0.036) and even in all APC patients (adjusted HR, 0.697; 95% CI, 0.491 to 1.990; p=0.044). Conclusion For APC patients receiving palliative chemotherapy, metformin treatment is associated with longer OS. Patients with DM tend to survive longer than those without DM.
참고문헌 (25)
- Kris MG, "Clinical cancer advances 2010 : annual report on progress against cancer from the American Society of Clinical Oncology", J Clin Oncol, 28, pp.5327~5347 (2010)
- Andre T, "Adenocarcinoma of the pancreas. General characteristics", Presse Med, 27, pp.533~536 (1998)
- Chiu CC, "Increased risk of gastrointestinal malignancy in patients with diabetes mellitus and correlations with anti-diabetes drugs : a nationwide population-based study in Taiwan", Intern Med, 52, pp.939~946 (2013)
- Kuuselo R, "Intersex-like(IXL)is a cell survival regulator in pancreatic cancer with 19q13 amplification", Cancer Res, 67, pp.1943~1949 (2007)
- Asano T, "Insulin receptor substrate is a mediator of phosphoinositide 3-kinase activation in quiescent pancreatic cancer cells", Cancer Res, 65, pp.9164~9168 (2005)
- Pannala R, "Prevalence and clinical profile of pancreatic cancerassociated diabetes mellitus", Gastroenterology, 134, pp.981~987 (2008)
- Huxley R, "Type-II diabetes and pancreatic cancer : a meta-analysis of 36 studies", Br J Cancer, 92, pp.2076~2083 (2005)
- Pannala R, "New-onset diabetes : a potential clue to the early diagnosis of pancreatic cancer", Lancet Oncol, 10, pp.88~95 (2009)
- Chari ST, "Pancreatic cancer-associated diabetes mellitus : prevalence and temporal association with diagnosis of cancer", Gastroenterology, 134, pp.95~101 (2008)
- Calle EE, "Diabetes mellitus and pancreatic cancer mortality in a prospective cohort of United States adults", Cancer Causes Control, 9, pp.403~410 (1998)
- Wakasugi H, "Clinical observations of pancreatic diabetes caused by pancreatic carcinoma, and survival period", Int J Clin Oncol, 6, pp.50~54 (2001)
- Chu CK, "Preoperative diabetes mellitus and longterm survival after resection of pancreatic adenocarcinoma", Ann Surg Oncol, 17, pp.502~513 (2010)
- Mizuno S, "Diabetes is a useful diagnostic clue to improve the prognosis of pancreatic cancer", Pancreatology, 13, pp.285~289 (2013)
- Li D, "Antidiabetic therapies affect risk of pancreatic cancer", Gastroenterology, 137, pp.482~488 (2009)
- Sadeghi N, "Metformin use is associated with better survival of diabetic patients with pancreatic cancer", Clin Cancer Res, 18, pp.2905~2912 (2012)
- Zheng W, "Association between body-mass index and risk of death in more than 1 million Asians", N Engl J Med, 364, pp.719~729 (2011)
- Zakikhani M, "Metformin is an AMP kinase-dependent growth inhibitor for breast cancer cells", Cancer Res, 66, pp.10269~10273 (2006)
- Quinn BJ, "Repositioning metformin for cancer prevention and treatment", Trends Endocrinol Metab, 24, pp.469~480 (2013)
- Hwang AL, "Metformin and survival in pancreatic cancer: a retrospective cohort study", Pancreas, 42, pp.1054~1059 (2013)
- Lee CK, "Cumulative metformin use and its impact on survival in gastric cancer patients after gastrectomy", Ann Surg (2015)[DOI]
- Cui Y, "Diabetes and pancreatic cancer", Endocr Relat Cancer, 19, pp.9~26 (2012)
- Hwang A, "Type 2 diabetes mellitus and survival in pancreatic adenocarcinoma : a retrospective cohort study", Cancer, 119, pp.404~410 (2013)
- Yuan C, "Survival among patients with pancreatic cancer and longstanding or recent-onset diabetes mellitus", J Clin Oncol, 33, pp.29~35 (2015)
- Nakai Y, "Clinical outcomes of chemotherapy for diabetic and nondiabetic patients with pancreatic cancer : better prognosis with statin use in diabetic patients", Pancreas, 42, pp.202~208 (2013)
- Sah RP, "New insights into pancreatic cancer-induced paraneoplastic diabetes", Nat Rev Gastroenterol Hepatol, 10, pp.423~433 (2013)