• Proportion of successes [ Designated as safety issue: No ]
  

• Survival time [ Designated as safety issue: No ]
  
• Time-to event analyses [ Designated as safety issue: No ]
  
• Time to disease progression/recurrence [ Designated as safety issue: No ]
  
• Time to recurrence [ Designated as safety issue: No ]
  
• Time to first progression [ Designated as safety issue: No ]
  
• Survival [ Designated as safety issue: No ]
  
• Bowel function as measured by the Patient Bowel Function (Uniscale) Questionnaire, the FACT Diarrhea Subscale and the Mayo Bowel Function Questionnaire [ Designated as safety issue: No ]
  

OBJECTIVES:

Primary

• Determine the pathological complete response rate in patients with stage II or III adenocarcinoma of the rectum treated with neoadjuvant celecoxib and capecitabine in combination with pelvic irradiation.

Secondary

• Determine the safety and tolerability of this regimen in these patients.
• Determine the rectal function of patients treated with this regimen.
• Determine the time to recurrence or progression and survival time of patients treated with this regimen.
• Correlate cellular and molecular markers in pretreatment tumor samples with response in patients treated with this regimen.

OUTLINE: This is a multicenter study.

• Neoadjuvant chemoradiotherapy: Patients receive oral celecoxib twice daily on days 1-7 and oral capecitabine twice daily on days 1-5. Patients undergo pelvic radiotherapy once daily on days 1-5. Courses repeat weekly for 5.5 weeks.
• Surgery: Patients undergo surgery 4-6 weeks after completion of neoadjuvant chemoradiotherapy.
• Adjuvant chemotherapy: Patients with a curative resection receive oral capecitabine twice daily on days 1-14. Treatment repeats every 21 days for up to 4 courses.

Treatment continues in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for 1 year and then every 6 months for 4 years.

PROJECTED ACCRUAL: A total of 23-55 patients will be accrued for this study within 10-28 months.

DISEASE CHARACTERISTICS:

• Histologically confirmed rectal adenocarcinoma

  • Clinical stage T3, N0, M0 OR any T, N1-3, M0 disease

• Treatment with neoadjuvant chemotherapy and pelvic radiotherapy is indicated

  • All disease must be encompassable within standard pelvic radiotherapy fields
• Distal border of the tumor must be at or below* the peritoneal reflection, defined as within 12 cm of the anal verge by endoscopy NOTE: *If a portion of the tumor is below the peritoneal reflection at the time of surgery, patients are eligible regardless of the distance of the tumor determined at endoscopy

• Tumor must be determined to be clinically resectable

  • Tumor may not be clinically fixed
  • Negative margins by routine examination of an unanesthetized patient
• Transmural penetration of tumor through the muscularis propria by CT scan, endorectal ultrasound, or MRI

• No distant metastatic disease

  • No evidence of tumor outside the pelvis, including any of the following:

    • Metastatic inguinal lymphadenopathy
    • Peritoneal seeding
    • Liver metastases

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-1

Life expectancy

• At least 6 months

Hematopoietic

• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3

Hepatic

• Bilirubin ≤ upper limit of normal (ULN)
• AST ≤ 3 times ULN
• Alkaline phosphatase ≤ 4 times ULN if AST < ULN

Renal

• Creatinine clearance ≥ 30 mL/min
• No renal impairment

Cardiovascular

• No congestive heart failure
• No symptomatic coronary artery disease
• No uncontrolled cardiac arrhythmias
• No myocardial infarction
• No history of transient ischemic attacks or stroke
• No other clinically significant cardiac disease

Gastrointestinal

• No bleeding peptic ulcer disease within the past 12 months
• No lack of physical integrity of the upper gastrointestinal tract
• No malabsorption syndrome
• No active inflammatory bowel disease
• Must be able to swallow study drugs

Other

• No dihydropyrimidine dehydrogenase deficiency
• No history of uncontrolled seizures
• No CNS disorders
• No clinically significant psychiatric illness that would preclude study compliance or giving informed consent
• No other malignancy within the past 5 years except basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
• No known sensitivity to NSAIDs, sulfonamides, or aspirin
• No other serious medical illness that would preclude study treatment
• No other conditions that would preclude study participation
• Must be able to tolerate major surgery that may include abdominal-perineal resection
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 30 days after study treatment

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• See Disease Characteristics
• No prior systemic anticancer chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• See Disease Characteristics
• No prior radiotherapy to the pelvis

Surgery

• See Disease Characteristics
• More than 3 weeks since prior major surgery and recovered

Other

• At least 7 days since prior nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin
• No other concurrent investigational drugs
• No other concurrent anticancer treatment
• No concurrent NSAIDs
• No concurrent primary prophylactic therapy for hand-foot syndrome
• No concurrent loperamide prophylaxis for diarrhea
• No concurrent sorivudine or brivudine