• Rate of pathologic complete response [ Designated as safety issue: No ]
  
• Effect of different chemoradiation-to-surgery intervals on rate of pathologic complete response, surgical difficulty, and postoperative complications [ Designated as safety issue: No ]
  

OBJECTIVES:

• Determine the rate of pathologic complete response (i.e., no evidence of residual tumor in the resected specimen) in patients with stage II or III rectal cancer treated with neoadjuvant chemoradiotherapy comprising radiotherapy and fluorouracil with or without combination chemotherapy comprising oxaliplatin, leucovorin calcium, and fluorouracil followed by surgical resection.
• Determine the effect of different chemoradiation-to-surgery intervals on the rate of pathologic complete response, surgical difficulty, and postoperative complications in these patients.

OUTLINE: This is a multicenter study. Patients are assigned to 1 of 4 treatment groups according to time of study enrollment.

• Group 1: Patients undergo chemoradiotherapy comprising radiotherapy once daily 5 days a week for 5 weeks and fluorouracil (5-FU) IV continuously over 24 hours 7 days a week for 5 weeks (weeks 1-5). Patients undergo surgical resection of the rectum in week 12. Patients then receive 9 courses of FOLFOX-6 chemotherapy comprising oxaliplatin, leucovorin calcium, and 5-FU or other chemotherapy off study as directed by the physician.
• Group 2: Patients undergo chemoradiotherapy as in group 1. Beginning in week 10, patients receive FOLFOX-6 chemotherapy comprising oxaliplatin IV over 2 hours and leucovorin calcium IV over 2 hours followed by bolus 5-FU on day 1 and 5-FU IV continuously over 46 hours on days 1 and 2. Treatment repeats every 14 days for 2 courses. Patients undergo surgical resection of the rectum in week 16. Patients then receive 7 additional courses of FOLFOX-6 chemotherapy or other chemotherapy off study as directed by the physician.
• Group 3: Patients undergo chemoradiotherapy as in group 1. Beginning in week 10, patients receive FOLFOX-6 chemotherapy comprising oxaliplatin, leucovorin calcium, and 5-FU as in group 2. Treatment repeats every 14 days for 4 courses. Patients undergo surgical resection of the rectum in week 20. Patients then receive 5 additional courses of FOLFOX-6 chemotherapy or other chemotherapy off study as directed by the physician.
• Group 4: Patients undergo chemoradiotherapy as in group 1. Beginning in week 10, patients receive FOLFOX-6 chemotherapy comprising oxaliplatin, leucovorin calcium, and 5-FU as in group 2. Treatment repeats every 14 days for 6 courses. Patients undergo surgical resection of the rectum in week 24. Patients then receive 3 additional courses of FOLFOX-6 chemotherapy or other chemotherapy off study as directed by the physician.

In all groups, treatment continues in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed for 1 month.

PROJECTED ACCRUAL: A total of 248 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically confirmed invasive adenocarcinoma of the rectum

  • Distal border of the tumor must be within 12 cm from the anal verge as measured on rigid proctoscopic exam

  • Stage II (T3, N0) or Stage III (any T, N1) disease confirmed by endorectal ultrasound (ERUS) or MRI

    • Patients with a high-grade obstruction that impedes the ERUS exam are eligible if staged by MRI
• Patients with synchronous or metachronous colorectal cancer are eligible provided they are treated for rectal cancer in accordance with this protocol
• Hereditary non-polyposis colorectal cancer allowed provided the patient meets all study eligibility criteria
• No metastatic disease or other primaries
• No locally recurrent rectal cancer
• No history of familial adenomatous polyposis

PATIENT CHARACTERISTICS:

• Karnofsky performance status 60-100%

• No history of any of the following significant cardiac diseases:

  • New York Heart Association class III-IV congestive heart failure
  • Symptomatic coronary artery disease
  • Uncontrolled arrhythmia
  • Myocardial infarction within the past 6 months
• No history of inflammatory bowel disease
• No history of uncontrolled seizures or clinically significant CNS disorders
• No history of psychiatric conditions or diminished capacity that would preclude giving informed consent or complying with the study
• No allergy and/or hypersensitivity to fluorouracil, leucovorin calcium, and/or oxaliplatin
• No history of difficulty or inability to take or absorb oral medications
• WBC ≥ 3,000/mm^3
• Absolute neutrophil count > 1,500/mm^3
• Hemoglobin > 9.5 g/dL
• Platelet count ≥ 100,000/mm^3
• Bilirubin ≤ 3mg/dL
• AST and ALT ≤ 2.0 times upper limit of normal (ULN)
• Alkaline phosphatase ≤ 2.0 times ULN
• Creatinine ≤ 1.5 times ULN
• No other malignancy within the past 5 years except basal cell carcinoma or carcinoma in situ of the cervix
• Not pregnant
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

• No prior radiotherapy to the pelvis
• No other concurrent investigational drugs
• No other concurrent anticancer therapy