Celecoxib, Fluorouracil, and Radiation Therapy in Treating Patients With Stage II or Stage III Rectal Cancer That Can Be Removed By Surgery

OBJECTIVES:

• Determine cyclo-oxygenase-2 (COX-2) overexpression in patients with resectable stage II or III rectal cancer treated with neoadjuvant celecoxib, fluorouracil, and radiotherapy.
• Determine whether administration of celecoxib, a COX-2 inhibitor, results in changes in tumor (COX-2 overexpressing) levels of eicosanoids but not in the surrounding normal tissue.
• Determine if there is a greater change in protein and gene expression in post-treatment biopsies when compared to pretreatment biopsies that are greater for tumor (COX-2 overexpression) than in surrounding normal tissue.
• Determine whether patients who express the greatest degree of change in gene and protein expression are those most likely to respond to therapy.
• Assess the toxicities of concurrent treatment with celecoxib, fluorouracil, and radiotherapy.

OUTLINE: This is a pilot study.

Patients receive oral celecoxib twice daily beginning 5 days prior to radiotherapy and continuing until completion of radiotherapy. Patients undergo radiotherapy 5 days a week for 5 weeks. Patients also receive concurrent fluorouracil IV continuously for 5 weeks. Patients undergo radical resection 4-10 weeks after completion of chemoradiotherapy.

Patients undergo tumor biopsy at baseline and then at the time of surgical resection. Patients also undergo blood and urine collection at baseline, 5 days after initiation of celecoxib, 7 days after initiation of celecoxib in combination with fluorouracil and radiotherapy, and at the time of surgical resection. The specimens are evaluated for COX-2 expression, eicosanoid production, and gene and protein expression using immunohistochemistry, microarray, and mass spectrometry.

After completion of study treatment, patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: Approximately 28 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically confirmed primary adenocarcinoma of the rectum

• Stage II or III disease
• Distal border of tumor must be at or below the peritoneal reflection

• Distal border of the tumor must be within 12 cm of the anal verge by proctoscopic exam
• Tumor must be clinically resectable
• Transmural penetration beyond muscularis propria by transrectal ultrasound
• No high-grade obstruction
• No evidence of metastatic disease

PATIENT CHARACTERISTICS:

• Karnofsky performance status 60-100%
• WBC ≥ 4,000/mm³
• Platelet count ≥ 150,000/mm³
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No other serious medical illness or psychiatric condition that would preclude study treatment
• No history of allergy to celecoxib or any other NSAIDs
• No history of allergy to sulfonamides
• No prior or concurrent malignancy except inactive noninvasive cervical carcinoma or skin cancer (excluding melanoma) or other cancer that has been disease free for ≥ 5 years

PRIOR CONCURRENT THERAPY:

• No prior radiotherapy to the pelvis
• At least 7 days since prior and no other concurrent COX-2 inhibitors or nonsteroidal anti-inflammatory drugs (NSAIDs)
• No concurrent warfarin except low-dose warfarin (1 mg/day)