Aflibercept +/- LV5FU2 in First Line of Non-resectalbe Metastatic Colorectal Cancers

Inclusion Criteria:

* Age ≥ 65 years
* General condition WHO ≤ 2
* Metastatic rectal or colonic adenocarcinoma, histologically proved on the primary tumour or a metastasis
* Metastases non-resectable and/or patient inoperable
* patients where a single agent chemotherapy combined with an anti-angiogenic agent is an appropriate approach
* At least one measurable target according to RECIST v1.1 criteria, no previously irradiated
* No previous treatment of the metastatic disease. Previous chemotherapy in an adjuvant situation completed 6 months or more before diagnosis of the metastasis is authorized.
* Adequate biological examination: Hb \> or = 9 g/dl, polynuclear neutrophils \> or = 1,500/mm3, platelets \> or =100,000/mm3, total bilirubin \< or = 1.5 x UNL, creatinine clearance, calculated according to Cockroft-Gault formula, \> 50 ml/min creatininemia \< 1.5 x UNL, ALP \< 5 x UNL, transaminases \< 5 x ULN, GGT\< 5 x UNL
* Proteinuria (strip) \< 2+; if \> or = 2+, test proteinuria over 24 hours which must be ≤ 1 g.
* Central genotyping of thymidylate synthase (TS) in blood DNA
* Patients treated with anticoagulants (coumadin, warfarin) can be included if the INR can be closely monitored. A change in anticoagulant treatment for low molecular weight heparin is preferable in order to respect indications
* Signed written informed consent obtained prior to inclusion

Exclusion Criteria:

* Patients with a primary tumour in place and presenting clinical symptoms (occlusion, haemorrhage)
* History of brain metastases, uncontrolled spinal cord compression, or carcinomatous meningitis or new evidence of brain or leptomeningeal disease.
* Uncontrolled hypercalcemia
* Uncontrolled hypertension (SBP \> 150 mmHg and DBP \> 100 mmHg) or history of hypertensive attacks or hypertensive encephalopathy
* Any progressive pathology not balanced over the past 6 months: hepatic insufficiency, renal insufficiency, respiratory insufficiency,
* Any of the following within 6 months prior to inclusion: myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft, NYHA class III or IV congestive heart failure, stroke or transient ischemic attack.
* Any of the following within 3 months prior to inclusion: Grade 3-4 gastrointestinal bleeding/hemorrhage, treatment resistant peptic ulcer disease, erosive oesophagitis or gastritis, infectious or inflammatory bowel disease, diverticulitis, pulmonary embolism or other uncontrolled thromboembolic event, wound or fractured bone
* Major surgery during the 28 days preceding the start of treatment
* Known acquired immunodeficiency syndrome (AIDS-related illnesses) or known HIV disease requiring antiretroviral treatment.
* Treatment with concomitant anticonvulsivant agents that are CYP3A4 inducers (phenytoin, phenobarbital, carbamazepine), unless discontinued \>7 days.
* Anti-tumoral treatments other than the trial treatments (chemotherapy, targeted therapy, immunotherapy)
* Macronodular peritoneal carcinosis (risk of perforation)
* Known DPD deficit
* Prior history of malignant haemopathy or cancer except those treated more than 5 years ago and considered to be cured, in situ cervical carcinomas and treated skin cancers (excluding melanoma)
* Patients on new oral anticoagulant therapy (rivaroxaban XARELTOR, apixaban ELIQUIS, dagigatran PRADAXA except if relay by vitamine K antagonist therapy)
* Any contraindication to the treatments used in the trial
* Impossibility of undergoing medical monitoring during the trial for geographic, social or psychological reasons