Preoperative Radiotherapy and Chemotherapy in Patients With Locally Advanced Rectal Cancer

Inclusion Criteria: * Previously untreated and pathologically proven adenocarcinoma of the rectum. * MRI staged T3 or T4, any N. * Lower border of tumour must be within 12 cm of anal verge. * Age greater than or equal to 18 years. * ECOG Performance Status 0-1 (Appendix 2) * Absolute neutrophil count greater than or equal to 1.5 x 109/L, haemoglobin greater than or equal to 90 g/L, and platelets greater than or equal to 100 x 109/L. * Adequate renal function: GFR greater than or equal to 55 mL/min (derived from serum creatinine e.g. using the Cockcroft-Gault formula or measured by radioisotopic techniques). * Bilirubin and ALT less than or equal to 1.5 x upper limit of normal. * No symptomatic peripheral neuropathy greater than or equal to grade 2. * Male or non-pregnant, non-lactating female. Patients on study with reproductive potential, or female partners with reproductive potential, must use an effective contraceptive. * Has provided written informed consent for participation in this trial Exclusion Criteria: * Presence of metastatic disease. * Prior pelvic radiotherapy * Febrile intercurrent illness or infection. * Previous history of unstable angina * Cardiac arrhythmia which in the opinion of the investigator would compromise the safe delivery of protocol treatment * Acute coronary syndrome even if controlled with medication * Myocardial infarction within the last 12 months * Concurrent treatment with other anti-cancer therapy. * Significant medical condition which in the opinion of the investigator would compromise the planned delivery of the chemotherapy and radiotherapy or which may be potentially exacerbated by these modalities. * Locally recurrent rectal cancer.