Influence of the Use of the Diabetic Drug Metformin on the Overall Survival and Treatment-related Toxicity in Advanced Stage Non-small Cell Lung Cancer Patients.

Study Overview
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Brief Summary
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There are preliminary data suggesting that patients suffering from non-insulin-dependent diabetes mellitus, treated with metformin, have improved local tumor control. A reduction in the tumor's hypoxia may be responsible for this phenomenon. Therefore, the aim of this study is to test the hypothesis in three cohorts of patients suffering from advanced stage non-small cell lung cancer and all undergoing concurrent radiochemotherapy: 1. Patients with diabetes mellitus treated with metformin only; 2. Patients with insulin-dependent diabetes mellitus not treated with metformin; 3. The remaining patients serving as controls. Furthermore, tumor and treatment-related parameters will be correlated with overall survival and morbidity.

Detailed Description
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There are preliminary clinical and preclinical data suggesting that patients suffering from non-insulin-dependent diabetes mellitus, treated with metformin, have improved local tumor control. The reduction in oxygen consumption of tumor cells and thus a relative reduction in the tumor's hypoxia may be responsible for this. Non-small cell lung cancer is the most frequent solid tumor in many Western countries and the number one cause of cancer-related death. Even though the introduction of concurrent chemoradiotherapy has improved local tumor control and thus overall survival, 5-year overall survival is still as low as 14%. Furthermore, many patients are not eligible to undergo concurrent treatment thus reducing their chances to defeat this disease. Additionally, concurrent chemoradiotherapy is associated with increased toxicity compared to sequential treatment. Therefore, alternative additives improving the effect of radiotherapy without increasing toxicity to an unbearable level are searched for. One possible pharmaceutical is metformin; many patients have been using it in the past without evident increased toxicity, it is cheap, and widely available. Thus, the aim of this study is to test the hypothesis that metformin increases overall survival without enhancing treatment-related toxicity. For this means, in three cohorts of patients suffering from advanced stage non-small cell lung cancer and all undergoing concurrent radiochemotherapy: 1. Patients with diabetes mellitus treated with metformin only; 2. Patients with insulin-dependent diabetes mellitus not treated with metformin; 3. The remaining patients serving as controls. Using Kaplan-Meier statistics as well as uni- and multivariate analysis, the overall survival and toxicity of these cohorts will be compared. Other potentially confounding factors will be tested as secondary endpoints.

Official Title
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Influence of Metformin Use on Treatment Outcome in NSCLC Patients

Conditions
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Non Small Cell Lung Cancer

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Advanced non-small cell lung cancer patients undergoing primary concurrent radiochemotherapy; patients treated with metformin or insulin will be analyzed as separate cohorts.
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Diabetes and metformin<br>Patients with diabetes mellitus treated with metformin only. | |
| Insulin-diabetes without metformin<br>Patients with insulin-dependent diabetes mellitus not treated with metformin | |
| Controlgroup<br>The remaining patients serve as control group. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of metformin use | Assessment of metformin use (in patients with diabetes mellitus) on overall survival in advanced stage NSCLC patients undergoing radiochemotherapy. | 2 years after radiotherapy | 
| Assessment of insulin use | Assessment of insulin use (in patients with diabetes mellitus) on overall survival in advanced stage NSCLC patients undergoing radiochemotherapy. | 2 years after radiotherapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall assessment of overall survival and toxicity factors | Composite outcome measure: Assessment of factors influencing overall survival and toxicity: Age Gender Performance status WHO TNM stage Histology Delivered radiation dose Total gross tumor volume Total planning target volume | 2 years after radiotherapy |