Dose-escalation Trial of Preoperative Radiotherapy and Concurrent Chemotherapy in Locally Advanced Rectal Cancer

Inclusion Criteria: * Pathologically proven diagnosis of adenocarcinoma of the rectum * Clinically determined to be stage T3 or T4,N0-N2, and M0 -staged by MRI or transrectal ultrasound of the rectum * Patients who are medically operable and who have resectable adenocarcinoma of the rectum at least \<11cm from the anal verge * Adequate liver/renal and haematological function. * Eastern Cooperative Oncology Group (ECOG) performance 0-2 * Age ≥ 18 years * Full blood count obtained within 2 weeks prior to registration on study, with adequate bone marrow function defined as follows: * Absolute neutrophil count (ANC) ≥ 1,800 cells/mm3 * Platelets ≥ 100,000 cells/mm3 * Haemoglobin ≥ 8.0 g/dl * Serum creatinine within normal institutional limits * Bilirubin within normal institutional limits * AST and ALT \< 2.5 x the IULN * Patient must sign study specific informed consent prior to study entry Exclusion Criteria: * Prior systemic chemotherapy for colorectal cancer; note that prior chemotherapy for a different cancer is allowable. * Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields * Any evidence of distant metastases (M1) * A synchronous primary colon carcinoma