Metformin and 5-fluorouracil for Refractory Colorectal Cancer.

Inclusion Criteria

• Histological diagnosis of metastatic colorectal adenocarcioma previously treated with at least two lines of chemotherapy (oxaliplatin and irinotecan regimens) if mutated KRAS or treated with at least 3 lines of chemotherapy (oxaliplatin, irinotecan and cetuximab) if KRAS wild type.
• Disease progression according to radiological or clinical assessment.
• Measurable disease.
• ECOG Performance 0-1.
• Age above 16 years.

• Normal organic function as defined for the following criteria:

  • Aspartate aminotransferase (AST), alanine aminotransferase (ALT) ≤ 2.5 times the upper normal limit of the local laboratory (LSN-LL);
  • Total serum bilirubin ≤ 2.0 x ULN-LL;
  • Absolute neutrophil count ≥ 1,500 / mm3;
  • Platelet count ≥ 100,000 / mm3;
  • Hemoglobin ≥ 8.0 g / dl;
  • Serum creatinine ≤ 1.5 x ULN-LL
• Written informed consent before enrollment

Exclusion Criteria

• Diabetic patients taking metformin.
• Patients already treated with mTOR inhibitors.
• Hypersensitivity to metformin, renal or hepatic impairment or other conditions that predispose to lactic acidosis.
• History of acute myocardial infarction in the last 6 months
• Serious illness or psychiatric condition.
• Current participation in other protocols with experimental drugs.
• Suspicion of dihidropirimida dehydrogenase(DPD)deficiency.
• Presence of active infection.
• No ability to ingest food orally.
• Patients with metastatic disease to CNS.
• Patients who underwent major surgery in the last 4 weeks.
• Patients who received chemotherapy in the last three weeks.
• Patients who underwent radiotherapy in the last 2 weeks or who received radiotherapy in the target lesion, if this is the only target lesion.
• Patients using oral anticoagulation (warfarin).
• Pregnant or lactating patients