Chemoradiation with Combination Chemotherapy for the Treatment of Rectal Cancer

Inclusion Criteria

• Pathologically proven diagnosis of adenocarcinoma of the rectum (located up to 15 cm from the anal verge). Diagnosis of rectal adenocarcinoma must be obtained by biopsy technique that does not completely excise the lesion (e.g., fine needle aspiration, core needle biopsy)
• Clinically determined to be stage II or III (T3-T4 or N1-N2 and M0)
• Contrast-enhanced imaging of the abdomen by computed tomography (CT); magnetic resonance imaging (MRI) rectal protocol; chest x-ray (or CT) of the chest. All within 56 days prior to registration to exclude distant metastases and provide local tumor stage
• Zubrod performance status 0-2
• Age >= 18
• Absolute neutrophil count (ANC) >= 1,200 cells/mm^3 (within 28 days prior to registration on study)
• Platelets >= 100,000 cells/mm^3 (within 28 days prior to registration on study)
• Hemoglobin >= 8.0 g/dl (Note: The use of transfusion or other intervention to achieve hemoglobin [Hgb] >= 8.0 g/dl is acceptable) (within 28 days prior to registration on study)
• Total bilirubin must be =< upper limit of normal (ULN) for the lab unless the patient has a bilirubin elevation > ULN to 1.5 x ULN due to Gilbert’s disease or similar syndrome involving slow conjugation of bilirubin (within 28 days before registration on this study)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) must be =< 3 x ULN for the lab (within 28 days before registration on this study) * If AST and/or ALT is >= ULN but =< 3 x ULN, serologic testing for hepatitis B and C must be performed and results for viral infection must be negative
• Serum creatinine =< 1.5 x ULN for the lab or calculated creatinine clearance > 30 mL/min (within 28 days before randomization)
• International normalized ratio (INR) of prothrombin time within 28 days before randomization must be =< ULN for the lab. Patients who are therapeutically treated with an agent such as warfarin may participate if they are on a stable dose and no underlying abnormality in coagulation parameters exists per medical history
• Patients with acquired immunodeficiency syndrome (AIDS-related illnesses) or known human immunodeficiency virus (HIV) disease must: * Have a CD4 count >= 200 cells/uL within 30 days before randomization * Be on a stable regimen of antiretroviral therapy * Have no evidence of opportunistic infections
• Pregnancy test (urine or serum beta-human chorionic gonadotropin [HCG]) done within 72 hours before randomization must be negative (for women of childbearing potential only). If urine pregnancy results are positive or cannot be confirmed as negative, a serum pregnancy test will be required

Exclusion Criteria

• Prior invasive malignancy (except non-melanomatous skin cancer) unless a) disease free for a minimum of 3 years or b) risk of recurrence is extremely low and unlikely to affect course over therapy over the next 12 months
• Prior systemic chemotherapy for current malignancy; note that prior chemotherapy for a different cancer is allowable
• Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields
• Severe, active comorbidity, defined as follows: * Unstable angina and/or congestive heart failure requiring hospitalization within the last 12 months * Transmural myocardial infarction within the last 6 months * Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration * Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days prior to registration * Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects * Evidence 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 * Known, existing uncontrolled coagulopathy. Patients on therapeutic anticoagulation may be enrolled provided that they have been clinically stable on anti-coagulation for at least 2 weeks * Evidence of grade 2 or greater peripheral neuropathy * Major surgery within 28 days of study enrollment (other than diverting colostomy)
• Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception; this exclusion is necessary because the treatment involved in this study may be significantly teratogenic
• Prior allergic reaction to oxaliplatin or capecitabine
• Any evidence of distant metastases (M1)
• A synchronous primary colon carcinoma
• Lack of physical integrity of the gastrointestinal tract (i.e., severe Crohn’s disease that results in malabsorption; significant bowel resection that would make one concerned about the absorption of capecitabine) or malabsorption syndrome that would preclude feasibility of oral chemotherapy (capecitabine)
• Participation in any investigational drug study within 28 days of study enrollment