This is a single arm phase II trial with combined celecoxib, tegafur-uracil, folinate and preoperative radiotherapy for patients with locally advanced rectal cancer. The primary end point is pathological complete response (pCR) rate. The secondary endpoints are toxicities of combined celecoxib and chemoradiation, negative resection margin rate, clinical tumor response by magnetic resonance imaging (MRI), sphincter preservation rate, disease-free survival and overall survival.

The primary objective is to determine the pathological complete response (pCR) of combining preoperative tegafur-uracil, folinate, radiation and celecoxib for locally advanced rectal cancer.

The secondary objectives of this study are to determine:

1. Toxicity profile of combining celecoxib, tegafur-uracil, folinate and preoperative radiation for locally advanced rectal cancer.
2. Negative resection margins (circumferential resection margin) rate.
3. Downstaging rate.
4. Sphincter preservation rate
5. Locoregional and distant failure rate.
6. Overall survival

Inclusion Criteria:

1. Patients with resectable or potentially resectable adenocarcinoma of the rectum.
2. Clinical stage by Magnetic Resonance Image (MRI) of pelvis, ultrasonography of liver and Chest X ray: AJCC T2 N1-2M0 or T3-4 N0-2M0 (patients who require diverting loop colostomy are eligible). Nuclear medicine study (whole body bone scan or PET scan) can be performed if clinically indicated.
3. Bi-dimensionally measurable disease by MRI, which can be done with pelvic array coil and intrarectal tube.
4. Age greater than 18 years and < 80 years, ECOG performance status < 2
5. Biopsy proven adenocarcinoma, superior margin of the tumor below the L5-S1 spine junction.
6. WBC > 3.5 x109/L, neutrophil count > 1.5x109/L, platelet count > 100x109/L, serum bilirubin < 1.25xULN (upper limit of normal), AST/ALT < 3x ULN, serum creatinine < 1.25xULN.
7. Informed consent signed.

Exclusion Criteria:

1. Distant metastasis, Prior pelvic irradiation, Inflammatory bowel disease, Medical conditions which preclude radical therapy.
2. History of malignancy within five years (except nonmelanoma skin cancer, CIN cervix).
3. Pregnancy.
4. Hypersensitivity to celecoxib, NSAID, sulfonamides or 5-FU.
5. Cardiovascular disease like congestive heart failure, symptomatic coronary artery disease, or myocardiac infarction.
6. History of peptic ulcer disease or NSAID-related gastrointestinal bleeding
7. Use of aspirin, other NSAID or celecoxib in the two weeks prior to study entry.
8. Patients taking warfarin or other anticoagulating medicine.