A Phase II Feasibility Translational Research Trial of Induction Chemotherapy Followed by Concomitant Chemoradiation in Patients with Clinical T3-T4 Rectal Cancer

Patient must have tumor tissue available for and must be willing to allow specimen submission for determination of treatment assignment. Histologically confirmed, locally advanced clinical T3-4 N0-2 M0 primary adenocarcinoma of the rectum based on the presence of at least one of the following: (1) clinically fixed tumors on rectal examination with tumor adherent to the pelvic sidewall and/or sacrum; (2) sciatica attributed to sacral root invasion with CT scan/MRI evidence of the lack of clear tissue plane; (3) hydronephrosis on CT scan or IVP of ureteric or bladder invasion as documented by cystoscopy and cytology or biopsy; (4) invasion into prostate, vagina or uterus. Transmural penetration of tumor through the muscularis propria must be demonstrated by EUS plus either CT or MRI within 28 days prior to reg. Distal border of tumor must be at or below peritoneal reflection, defined as within 12 centimeters of the anal verge by proctoscopic examination. Measurable disease. No clinical evidence of high-grade large bowel obstruction, unless a diverting colostomy has been performed. No prior intra-operative RT or brachytherapy and no plans for such therapy while on protocol tx. No prior chemo for colon or rectal cancer. No prior pelvic irradiation therapy. Zubrod PS 0-2. Must be able to swallow oral meds. ANC >/= 1,500/mm3; WBC >/= 3,500/mcl; platelets >/= 100,000/mcl; bilirubin </= 1.5 x ULN; SGOT/SGPT </= 2.5 x ULN; alkaline phosphatase </= 2.5 x ULN. Measured creatinine clearance </= 1.5 x ULN or estimated creatinine clearance > 50 ml/min. No active inflammatory bowel disease or other serious illness. No prior unanticipated severe reaction to fluoropyrimidine therapy, no known sensitivity to 5-FU, oxaliplatin or irinotecan, and no known DPD deficiency. Must not be pregnant or nursing. Women/men of reproductive potential must have agreed to use effective contraceptive method. No prior malignancy except adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer or other cancer from which the patient has been disease-free for five years.