Systemic Oxaliplatin or Intra-arterial Chemotherapy Combined With LV5FU2 +/- Irinotecan and an Target Therapy in First Line Treatment of Metastatic Colorectal Cancer Restricted to the Liver

Prior treatment

• Patient immediately eligible for a curative therapy (surgical and/or percutaneous) after discussion in CPR
• Following alterations in the 6 months prior to inclusion: myocardial infarction, angina, severe/unstable angina, coronary artery bypass surgery, congestive heart failure NYHA class II, III or IV, stroke or transient ischemic attack
• Abdominal or major extra-abdominal surgery (except diagnostic biopsy) or irradiation in the 4 weeks before starting the treatment

Other illness

• Contraindications specific to the installation of a KTHIA: thrombosis of the hepatic artery, arterial vascular anatomy may compromise a secondary hepatic resection.
• Hypertension not controlled by medical treatment (SBP \> 140 mmHg and/or DBP\> 90 mmHg with blood pressure taken according to the diagram of the HAS)
• A history of abdominal fistula, gastrointestinal perforation, intra-abdominal abscess or active gastrointestinal bleeding in the 6 months preceding the start of treatment
• Progressive gastroduodenal ulcer, wound or fractured bone
• Transplant patients, HIV positive or other immune deficiency syndromes
• Any progressive pathology not balanced over the past 6 months: hepatic failure, renal failure, respiratory failure
• Patient with interstitial pneumonitis or pulmonary fibrosis
• History of chronic diarrhea or inflammatory disease of the colon or rectum, or unresolved occlusion or sub-occlusion in symptomatic treatment
• History of malignant pathologies during the past 5 years except basocellular skin carcinoma considered in complete remission or in situ cervical carcinoma, properly treated
• Any known specific contraindication or allergy or hypersensitivity to the drugs used in the study (cf RCP Appendix 7)

Lab values

• QT/QTc range \> 450 msec for men and \> 470 msec for women

Age

• Lack of effective contraception in patients (men and/or women) of childbearing age, pregnant or breastfeeding women, women of childbearing age not having had a pregnancy test

Other

• Peripheral neuropathy \> 1
• Patient already included in another clinical trial with an experimental molecule
• Known deficit in DPD
• K+ \< LNL, Mg2+ \< LNL, Ca2+ \< LNL
• Persons deprived of liberty or under supervision
• Impossibility of undergoing medical monitoring during the trial for geographic, social or psychological reasons

• Histologically proven colorectal adenocarcinoma with hepatic metastasis(es)
• At least one measurable hepatic metastasis according to the criteria RECIST v1.1
• No other metastatic sites except lung nodules if number ≤ 3 and \< 10 mm
• RAS mutation status known (determination of KRAS mutation (exons 2,3 and 4) and determination of the NRAS mutation (exons 2,3 and 4))
• Age ≥ 18
• WHO ≤ 2 (Appendix 4)
• No prior treatment by chemotherapy except perioperative or adjuvant chemotherapy discontinued for more than 12 months
• Life expectancy \> 3 months
• PNN \> 1500/mm3, platelets \> 100 000/mm3, Hb \> 9 g/dLq
• Bilirubin \< 25 mmol/L, AST \< 5x ULN, ALT \< 5 x ULN, ALP \< 5 x ULN, TP \> 60%, proteinuria from 24H \< 1 g
• Creatinine clearance \> 50 mL/min according to MDRD formula (Appendix 4)
• Patient affiliated to a social security scheme
• Patient information and signature of the informed consent