Inclusion Criteria:

• Age over 18.
• Histological diagnosis of adenocarcinoma of rectum.

• Locally advanced/ poor prognosis primary rectal cancer defined by MRI criteria of any of the categories below;

  • Tumour within 2 mm of mesorectal fascia ie circumferential resection margin threatened
  • Any T3 tumour at/below levatores
  • T3c tumour at any other level ie tumour extends >5 mm into peri-rectal fat
  • T4 tumour
  • Any T stage with 4 or more involved lymph nodes
• WHO performance status 0, 1 or 2.
• No evidence of metastatic disease as determined by CT scan of chest, abdomen, pelvis or other investigations such as PET scan or biopsy if required.
• Adequate bone marrow function with platelets > 100 X 109/l; WBC > 3 X 109/l; neutrophils > 1.5 X 109/l
• Normal renal function, with serum creatinine within the normal range or calculated creatinine clearance >50 ml/min.
• Adequate hepatic function with serum total bilirubin < 1.5 X upper limit of normal range.
• No concurrent uncontrolled medical conditions
• No previous malignant disease other than non-melanotic skin cancer or carcinoma in situ of the uterine cervix
• Adequate contraceptive precautions if relevant
• Informed written consent

Exclusion Criteria:

• Medical or psychiatric conditions that compromise the patient’s ability to give informed consent
• Presence of metastatic disease or recurrent rectal tumour
• Renal impairment (creatinine clearance<30 ml/min)
• Pregnancy or breast feeding
• Patients with a lack of physical integrity of the upper gastrointestinal tract, or known malabsorption syndromes
• Participation in any investigational drug study within the previous 4 weeks.
• Clinically significant (i.e. active) cardiac disease (e.g. congestive heart failure, symptomatic coronary artery disease and cardiac arrhythmia even if controlled with medication) or myocardial infarction within the last 12 months)
• Patients with any symptoms or history of peripheral neuropathy.
• Prior pelvic radiotherapy