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Metformin- Antitumor activity
Introduction:
Diabetes and pancreatic cancer have an intertwined relationship. It is observed that long-term type II diabetes mellitus has been associated with increased risk for pancreatic cancer. On the other hand patients with pancreatic cancer often have a high prevalence (80%) of concurrent diabetes or impaired glucose tolerance. The biologic mechanisms most frequently shared by diabetes and pancreatic cancer are Insulin resistance and inflammation. Recent epidemiologic investigations conducted in cohorts of patients with diabetes and patients with cancer showed that the use of metformin, a common antidiabetic drug, was associated with lower risk of cancer or lower cancer mortality compared with the use of insulin or insulin secretagogues. Data from two clinical studies also suggest that metformin use may have clinical benefits for patients with diabetes and cancer. Purpose:
The aim of this study was to determine whether metformin use has a survival benefit in patients with pancreatic cancer. Experimental design:
Patients with pathologically confirmed pancreatic adenocarcinoma and pre-cancer diagnoses of diabetes mellitus were included in this retrospective cohort study. All patients were identified from a case–control study of pancreatic cancer conducted at The University of Texas MD Anderson Cancer Center (Houston, TX) from January 2000 to May 2009. Personal interviews and medical record review were used to collect information on diabetes history, including treatment modalities and clinical outcome of pancreatic cancer. Assumptions:
 To ensure adequate study power, patients who had ever received metformin and those who had never received metformin were compared, regardless of the dose and duration of metformin use and other combinational therapies they had received.  OS time was calculated from the date of diagnosis to the date of death.  Living patients were censored at the time of data analysis. Results:
 302 patients identified.  No significant differences in demographic or major clinical characteristics between the patients who had received metformin (n = 117) and those who had not (n = 185).  2-year survival rate was 30.1% for the metformin group and 15.4% for the non- metformin group (P = 0.004, Ẍ 2 test).  The median overall survival (OS) time was 15.2 months for the metformin group, and 11.1 months for the non-metformin group (P= 0.004, log-rank test).  Metformin users had a 32% lower risk of death; the HR (95% confidence interval) was 0.68 (0.52–0.89) in a univariate model (P = 0.004), 0.64 (0.48–0.86) after adjusting for other clinical predictors (P = 0.003), and 0.62 (0.44–0.87) after excluding insulin users (P = 0.006).  The beneficial effect of metformin was seen in all disease stages but was statistically significant only in patients with nonmetastatic disease. Strength:
This study included large sample size of patients with diabetes and pancreatic cancer and detailed clinical information were analyzed. Limitations:
As it is a retrospective study, it is associated with recall bias and information bias. This study did not take into consideration the impact of the dose at which metformin was administered, the joint effect of other antidiabetic agents, or the glycemic control status. (However, the survival differences in metformin and non-metformin group could not be explained by the patient performance status or insulin use.) Conclusions:
This study adds supporting evidence for the antitumor activity of metformin, however future prospective studies are required to validate the results of this study; assess the dose/duration effect and also address the safety and efficacy of this treatment in nondiabetic patients. Metformin Use Is Associated with Better Survival of Diabetic Patients with Pancreatic
Cancer; Navid Sadeghi, James L. Abbruzzese, Sai-Ching J. Yeung, et al; Clin Cancer
Res Published OnlineFirst March 31, 2012.
Commentary by:
Dr. Sudeep Gupta, Medical Oncologist

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