Trial of Celecoxib With Preoperative Chemo- Radiation for Locally Advanced Rectal Cancer

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:

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

Inclusion criteria

• Patients with resectable or potentially resectable adenocarcinoma of the rectum.
• 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.
• Bi-dimensionally measurable disease by MRI, which can be done with pelvic array coil and intrarectal tube.
• Age greater than 18 years and < 80 years, ECOG performance status < 2
• Biopsy proven adenocarcinoma, superior margin of the tumor below the L5-S1 spine junction.
• 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.
• Informed consent signed.

Exclusion criteria

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