A phase II study to investigate combination of chemo-radiotherapy with metformin in patients with Locally Advanced Non-Small Cell Lung Cancer (LA-NSCLC)
It is estimated that in 2012 in Canada 25,600 people were diagnosed with lung cancer and more than 20,000 died from it. More than 80% of lung cancer patients are diagnosed with NSCLC which often presents at advanced stages in patients with poor health who cannot tolerate surgical treatment. Such patients are treated with radiotherapy (RT) and Chemotherapy (CT) (CRT). Unfortunately, NSCLC exhibits resistance to CRT, which leads to poor tumour control and less than 17% 5 year survival. Metformin is an economical and well tolerated anti-diabetic medication. It is used by more than 120 million patients worldwide and it is well tolerated by non-diabetic individuals also. Metformin is associated with decreased cancer risk, improved chemotherapy responses in breast cancer and now it is investigated in breast cancer patients. We have completed pre-clinical laboratory research which showed that NSCLC cells show high sensitivity to metformin. We observed that metformin, used at doses that can be achieved safely in humans, sensitizes NSCLC to RT and inhibits the growth of human NSCLC tumours in animals. Here we propose to examine whether addition of metfomrin to CRT can improve treatment results in patients with NSCLC compared to those treated with CRT alone. Patients with advanced NSCLC who will be treated with CRT will receive additional oral treatment with metformin or not. Survival free of disease progression and side effects of treatment will be monitored. Blood glucose and insulin levels will be monitored during the treatment and blood samples will be taken to examine drug levels and biological activity of MET. This study provides a valuable opportunity to examine whether an economical, well tolerate and promising medication can improve the results of standard therapy in patients with advanced lung cancer who otherwise have a poor prognosis. If positive this study will provide the first clinical evidence of a new therapeutic option for lung cancer patients.