The aims of the trial are (1) to determine the tolerability rate in the setting of a multi-centre study and (2) to determine secondary tolerability endpoints, toxicity rates and complete pathologic response rate in patients with locally advanced rectal cancer who are treated with an integrated preoperative radiotherapy with FOLFOX chemotherapy regimen.

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.