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 transrectalultrasound of the rectum

• Patients who are medically operable and who have resectable adenocarcinoma of therectum 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 adequatebone 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 adifferent cancer is allowable.

• Prior radiotherapy to the region of the study cancer that would result in overlap ofradiation therapy fields

• Any evidence of distant metastases (M1)

• A synchronous primary colon carcinoma