Combination of Oxaliplatin, Capecitabine, and Celecoxib With Concurrent Radiation for Rectal Cancer

Inclusion Criteria:

• All patients 18 years of age or older, with biopsy proven T3-4N0-2M0 rectal cancer are eligible.
• life expectancy of at least 2 years.
• Zubrod performance status of 0-2.
• Patients must be able to sign an informed consent.
• adequate bone marrow function: peripheral granulocyte count of > 1,500 cells/mm3 and platelet count >100,000/mm3, hemoglobin > 10 gm/dl and absence of a regular red blood cell transfusion requirement.
• adequate hepatic function with a total serum bilirubin < 1.5 x ULN; alkaline phosphatase, ALAT, and ASAT < 2.5 x ULN; and adequate renal function as defined by a calculated creatinine clearance > 50 ml/min [Cockroft-Gault].
• other initial cancer diagnosis more than five years ago without evidence of residual or recurrent disease
• prior diagnosis of squamous or basal cell carcinoma of skin,no active disease at the time of enrollment.

Exclusion Criteria:

• known metastases
• Pregnant or lactating women. Women/men of childbearing potential not using a reliable and appropriate contraceptive method.
• may receive no other concurrent chemotherapy or radiation therapy during this trial.
• severe medical problems such as uncontrolled diabetes mellitus or cardiovascular disease or active infections
• Prior pelvic radiation
• known active inflammatory bowel disease, Crohn's disease or ulcerative colitis.
• medical conditions that would preclude the patient from definitive surgery at the end of concurrent chemoradiation
• Serious, uncontrolled, concurrent infection(s).
• Prior severe reaction to fluoropyrimidine therapy, or known hyper-sensitivity to 5-fluorouracil or known dihydropyrimidine dehydrogenase (DPD) deficiency.
• Treatment for other carcinomas within the last five years, except cured non-melanoma skin and treated in-situ cervical cancer.
• Participation in any investigational drug study within 4 weeks preceding the start of study treatment.
• Clinically significant cardiac disease or myocardial infarction within the last 12 months.
• History of uncontrolled seizures, central nervous system disorders or psychiatric disability judged by the investigator to be clinically significant, precluding informed consent, or interfering with compliance of oral drug intake.
• Other serious uncontrolled medical conditions that the investigator feels might compromise study participation.
• Major surgery <4 weeks of the start of study treatment, without complete recovery.
• Lack of physical integrity of the upper gastrointestinal tract or malabsorption syndrome.
• Known, existing uncontrolled coagulopathy

• Any of the following laboratory values:

  • Abnormal hematologic values (neutrophils < 1.5 x 10^9/L, platelet count < 100 x 10^9/L, hemoglobin < 10 gm/dl)
  • Impaired renal function (estimated creatinine clearance <50 ml/min as calculated with Cockroft-Gault equation.
  • Serum total bilirubin > 1.5 x upper normal limit.
  • ALAT, ASAT > 2.5 x upper normal limit (or > 5 x upper normal limit in the case of liver metastases).
  • Alkaline phosphatase > 2.5 x upper normal limit (or > 5 x upper normal limit in the case of liver metastases or > 10 x upper normal limit in the case of bone disease).
• Unwillingness to give written informed consent.
• Unwillingness to participate or inability to comply with the protocol for the duration of the study.
• History of allergic reactions, hypersensitivity reactions to aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), or sulfonamides