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Patients with Advanced Pancreatic Cancer when Treated with Metformin Showed Increased Survival Rates

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Positive Overall Survival Rate in Patients With Advanced Pancreatic Cancer Treated On Metformin For Diabetes Mellitus

Introduction

Pancreatic cancer (PC) is the fourth common cause of cancer death in both Asian and western countries. At the time of diagnosis, only 10%-20% of patients are eligible for curative surgery. PC is an aggressive malignancy with a 5-year survival rate of < 5%. Diabetes mellitus (DM) is linked as a risk factor in a number of cancers. Although the mechanisms of increased incidence of cancer with DM are not fully understood, insulin resistance, leading to hyperinsulinemia, causes up-regulation of insulin-like growth factor-I (IGF-I) signaling pathway to increase proliferation and invasion of cancer cells and decrease apoptosis.

Purpose

A causal relationship between diabetes mellitus (DM) and pancreatic cancer is well established. However, in patients with advanced pancreatic cancer (APC) who receive palliative chemotherapy, the impact of DM on the prognosis of APC is unclear.

Objective

To understand the impact of Diabetes mellitus (DM) on the prognosis of advanced pancreatic cancer (APC)

Materials and Methods

Data collection and categorization precisely defined DM disease status was a requirement, stipulated as follows:

  1. self-reported diabetic history
  2. Ongoing treatment with anti-diabetic medication(s)
  3. Qualification as DM during the follow-up period

Date of diagnosis was the date that locally advanced PC (LAPC) or metastatic/recurrent PC (MPC) was confirmed. Patient age, performance status, DM status, anti-diabetic treatments, body weight, body mass index (BMI), smoking history, and initial laboratory data were assessed.

Statistical analysis

The study endpoint is overall survival (OS) defined as the period from diagnosis of APC to death from any cause. We calculated median OS using the Kaplan-Meier method. Between-group differences in demographic and clinical data were evaluated using Fisher exact test for categorical variables. For the effect of multiple factors on survival, the hazard ratio (HR) and its 95% confidence interval (CI) were evaluated using Cox proportional hazards model. The survival of the two groups was compared using the log-rank test. All tests were 2-sided, and p-values of “0.05 were considered statistically significant.

Results

1. Patient characteristics

A total of 349 patients were enrolled. By definition, 183 patients (52.4%) had concurrent DM, whether preexisting (160 patients) or subsequent (23 patients). Of those with preexisting DM, 87 qualified as remote-onset and 73 as recent-onset. The majority of patients with concurrent DM (134/183, 73.2%) were taking anti-diabetic medication including metformin (56/134, 41.8%), sulfonylurea (62/134, 45.5%), and insulin (43/134, 32.1%).

2. Patient comparisons (DM vs. non-DM)

The OS of the DM group was 8.4 months (95% CI, 6.8 to 10.0 months), compared with 7.5 months (95% CI, 6.3 to 8.7 months) for the non-DM group (p=0.041, log-rank test). The clinical characteristics of patients with APC were also compared in order to determine other factors causing the difference of OS between DM and non-DM subsets. In the DM group, more patients were past the age of 60 years than in the non-DM group (59.6% vs. 38.0%, p < 0.001). ECOG PS, cancer extent, cancer antigen 19-9 level, and response to chemotherapy, etc. did not differ significantly between groups, although patients with DM showed a tendency for greater weight loss at diagnosis (change in BMI ! 1, p=0.067).

Conclusion

It was shown that metformin use is a favorable prognostic factor in APC patients receiving palliative chemotherapy. We also showed the tendency that patients with DM survived longer than those without DM.

Reference

Younak choi et al The Impact of Diabetes Mellitus and Metformin Treatment on Survival of Patients with Advanced Pancreatic Cancer Undergoing Chemotherapy. Cancer Res Treat. 2016 Jan;48(1):171-9. doi: 10.4143/crt.2014.292.

Available at: http://www.ncbi.nlm.nih.gov/pubmed/25779362/

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