Combination of Metformin to Neoadjuvant Radiochemotherapy in the Treatment of Locally Advanced Rectal Cancer.

Inclusion Criteria:

1. Patient with an adenocarcinoma of the low or middle rectum.
2. T3 or T4 stage (T evaluated by MRI and / or echo-endoscopy).
3. Absence of distant metastasis.
4. Patient requiring a radiochemotherapy.
5. Correct hematological conditions : Neutrophils ≥ 1500 G / L, platelets ≥ 100 000 G / L.
6. Age ≥ 18 years
7. Performance status (WHO) ≤ 2
8. Lactatemia ≤ Higher standard of the sampling laboratory.
9. For women of childbearing age, a contraceptive method is mandatory for the entire duration of the study.

Exclusion Criteria:

1. Other histologies such as squamous cell carcinoma, neuroendocrine tumors, melanomas, etc.
2. History of lactic acidosis.
3. Any diabetes (According to the WHO definition : fasting plasma glucose (FPG) \> 1.26 g / L-1).
4. Ongoing antidiabetic treatment such as

   * Biguanides, hypoglycemic sulfamides, glinides, GLP-1 analogue, gliptins, alpha-glucosidase inhibitors
   * Insulin or insulin analogues
5. Hypersensitivity to capecitabine or to any of the excipients or to fluorouracil.
6. History of severe and unexpected reactions to a fluoropyrimidine therapy.
7. Patient with known deficiency to the dihydropyrimidine dehydrogenase (DPD).
8. Hypersensitivity to metformin or to any of the excipients.
9. Renal failure or impaired renal function (creatinine clearance \< 60 ml / min).
10. Severe infection.
11. Acute or chronic disease which may cause tissue hypoxia such as heart or respiratory failure or recent myocardial infarction (\< 6 months).
12. Hepatic insufficiency, acute alcohol intoxication, alcoholism.
13. Psychiatric inability to give consent.
14. Contraindication to radiation therapy and/or chemotherapy.
15. Treatment with sorivudine or its chemically related analogues, such as brivudine.
16. Patient under tutorship or guardianship.
17. Pregnant or breastfeeding women.