Erbitux Study of CPT11, Oxaliplatin, UFToral Targeted Therapy

Inclusion Criteria: * Histologically confirmed adenocarcinoma of the colon or rectum. * Patients must not have a mutation of K-ras * Inoperable metastatic or locoregional disease (synchronous or recurrence) * No previous chemotherapy for established metastatic disease (adjuvant chemotherapy must have been completed more than 6 months prior to trial entry) * Measurable or evaluable disease * Bone marrow function: neutrophil count \>1.5 x109/l and platelet count \>150 x109/l * Hepatobiliary function: serum bilirubin \<1.5 x upper limit of normal (ULN); ALP \<5 x ULN; transaminase (AST or ALT) \<3 x ULN.(≤ 5 if liver mets are present) * Renal function: estimated creatinine clearance \>50 ml/min, or measured Glomerular filtration rate (GFR) (EDTA or creatinine clearance) in normal range * ECOG performance status 0-1 and considered fit and able to undergo all possible treatments * For women of child-bearing potential a negative pregnancy test is required and adequate contraceptive precautions such as a sheath for their partner must be used * For men - adequate contraception such as a sheath must be used * Patients must give written, informed consent * Life expectancy ≥ 3 months. Exclusion Criteria: * Patients that have a K-ras mutation * Concurrent uncontrolled medical illness, or other previous or current malignant disease likely to interfere with protocol treatments or comparisons * Partial or complete bowel obstruction * Prior EGFR antibody therapy * Age \<18 * Chronic diarrhoea or inflammatory bowel disease * Known Pyruvate Dehydrogenase Phosphatase (DPD) deficiency * Gilbert's syndrome or other congenital abnormality of biliary transport * Previous transplant surgery, requiring immunosuppressive therapy * Regular / uncontrolled angina or cardiac arrhythmias * Clinically relevant coronary artery disease. History of Myocardial infarction in the last 12 months * Previous investigational agent in the last 4 weeks * Metastatic disease to brain * Any pregnant or lactating women * Patients receiving therapy with haloginated antiviral drugs (eg: sorivudine) * Patients who have experienced life-threatening toxicities with fluoropyrimidines treatment * Patients suffering from any condition that may affect the absorption of UFT or folinic acid. * Patients with known deficiency of or are on inhibitors of cytochrome P450 2A6 * Patients who have previously had radiotherapy to the abdomen or pelvis in the last 6 months * Any medical or psychological condition that in the opinion of the investigator would not enable the patient to complete the study or knowingly give informed consent