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