(Ir)relevance of Metformin Treatment in Patients with Metastatic Pancreatic Cancer: An Open-Label, Randomized Phase II Trial

Quyen Bach, Mercer University College of Pharmacy

 

Metformin is a commonly prescribed medication for the treatment for type 2 diabetes; it is stated to lower both glucose and insulin levels.1 Metformin has been proven to have properties of potential oncologic relevance, such as reducing systemic insulin and insulin-like growth factor (IGFI) levels and has direct growth-inhibitory action on cancer cells.2

Due to these effects, it is stated that this medication might be repurposed for indications in oncology, including for use in pancreatic cancer.

(Ir)relevance of Metformin Treatment in Patients with Metastatic Pancreatic Cancer: An Open-Label, Randomized Phase II Trial3
Design Single-center, prospective, open-label, randomized, phase II; N = 60
Objective To test the efficacy of adding metformin to systemic chemotherapy in patients with metastatic pancreatic cancer
Study Groups Metformin (n = 31); no metformin (n = 29)
Methods Patients with pathology-confirmed diagnosis of metastatic pancreatic adenocarcinoma were randomized to receive metformin 2g PO daily or not in association with standard four-drug chemotherapy regimen including cisplatin, epirubicin, capecitabine, gemcitabine (PEXG).
Duration August 2010 to January 2014
Primary Outcome Measure The progression-free survival at 6 months from treatment start (PFS-6)
Baseline Characteristics   PEXG (n = 29) PEXG (n = 31) p value
Mean age (yr) 63 64 0.67
Gender (M/F) 13/16 17/14 0.6
Primary tumor location
   Head 17 (59%) 14 (45%) 0.31
   Body/tail 12 (41%) 17 (55%)  
Metabolic variables
   Diabetes treated 4 (14%) 4 (13%) 0.85
   Diabetes undiagnosed 7 (24%) 8 (26%)  
Results   PEXG (n = 29) 95% CI PEXG + metformin (n = 31) 95% CI p value
PFS-6 15 (52%) 33 – 69 13 (42%) 24 – 59 0.61
Adverse Events Common Adverse Events: N/A
Serious Adverse Events: N/A
Percentage that Discontinued due to Adverse Events: N/A
Study Author Conclusions Addition of metformin at the dose commonly used in diabetes did not improve outcome in patients with metastatic pancreatic cancer treated with standard systemic therapy.
 

 

 

Although adding metformin did not result in a positive impact on patients’ survival, this study showed that metformin was well tolerated when combined with chemotherapy. Given the small sample of patients and the presence of potential confounding biases, such as being open-label and conducted at a single institution, more studies are needed to better understand a potential antagonism between metformin and cancer progression.

 

References

  1. Stern RJ, Murphy EJ. Metformin as initial oral therapy in type 2 diabetes. JAMA 2015; 313:2484-5.
  2. Pollak M. Insulin and insulin-like growth factor signaling in neoplasia. Nat Rev Cancer 2008;8:915-28.
  3. Reni M, Dugnani E, Cereda S, et al. (Ir)relevance of Metformin Treatment in Patients with Metastatic Pancreatic Cancer: An Open-Label, Randomized Phase II Trial. Clin Cancer Res. 2016;22(5):1076-85.
Advertisements

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out / Change )

Twitter picture

You are commenting using your Twitter account. Log Out / Change )

Facebook photo

You are commenting using your Facebook account. Log Out / Change )

Google+ photo

You are commenting using your Google+ account. Log Out / Change )

Connecting to %s