Capecitabine, Oxaliplatin, and Radiation Therapy in Treating Patients With Stage II or Stage III Anal Cancer

Inclusion Criteria: 1. Previously untreated patients with histologically proven squamous cell carcinoma of the anal canal. 2. American Joint Committee on Cancer (AJCC) stage II-IIIB (TX 1-4, NX, MO). 3. Age \>/= 16 yrs old. 4. Eastern Cooperative Oncology Group (ECOG) Performance Scale (PS) 0-1. 5. Adequate organ function including: Absolute neutrophil Count (ANC) \>/= 1,500/uL, Platelets \>/= 100,000/uL, Total bilirubin \</= 1.5 \* upper limit of normal (ULN), aspartate aminotransferase (AST or SGOT)/alanine aminotransferase (ALT or SGPT) \</= 3 \* ULN, Creatinine \</= 1.5mg/dL or Creatinine Clearance (CrCL) \>/= 50 cc/min. 6. Patients may have measurable or non-measurable disease. Patients with measurable disease, as defined by the modified Response Evaluation Criteria in Solid Tumors (RECIST) criteria, have at least one lesion that can be accurately measured in at least one dimension with longest diameter to be recorded \>/= 20 mm using conventional techniques or \>/= 10 mm with spiral CT scan (with minimum lesion size no less than double the slice thickness). Lesions seen on colonoscopy or barium studies are not considered measurable lesions. 7. A negative pregnancy test in all women of child-bearing potential, within two weeks of initiating treatment. 8. The effects of oxaliplatin and capecitabine on the developing human fetus at the recommended therapeutic dose are unknown. For this reason and because cytotoxic agents are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. 9. Ability to understand and the willingness to sign the written informed consent/authorization document. Exclusion Criteria: 1. Prior chemotherapy with oxaliplatin, capecitabine, or 5-fluorouracil. 2. Prior radiation to the pelvis. 3. Prior surgery for anal cancer excluding prior biopsy. 4. Known history of dihydropyrimidine (DPD) deficiency. 5. Known history of hypersensitivity to platinum-containing compounds. 6. Peripheral neuropathy of \>/= grade 2 by Common Terminology Criteria for Adverse Events (CTCAE) 3.0. 7. Calculated creatinine clearance (CrCl) \< 50 cc/min. 8. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit adherence with study requirements. 9. Gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for intravenous (IV) alimentation. 10. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with oxaliplatin or capecitabine, breast feeding should be discontinued. 11. Because of the known interaction of capecitabine and coumadin, patients taking coumadin will be ineligible. Patients will be requested to discontinue coumadin and utilize Lovenox if agreeable. Patients must have discontinued coumadin for 7 days before initiating therapy. 12. No prior malignancies (excluding non-melanomatous skin neoplasms) over the past 5 years. 13. HIV-positive patients receiving combination anti-retroviral therapy are excluded from this study because of possible pharmacokinetic interactions with capecitabine or oxaliplatin. This exclusion is for patient safety since patients with immune deficiency are at increased risk of lethal infections when treated with marrow-suppressive therapy, and because very few HIV-positive anal canal cancer patients are seen at this institution. This hinders us from accruing enough patients to adequately test the safety of this regimen in this population. 14. Patients with symptomatic pulmonary fibrosis.