Chemotherapy and Radiation Therapy Before Surgery Followed by Capecitabine With or Without Oxaliplatin in Treating Patients With Locally Advanced Rectal Cancer

OBJECTIVES: Primary * Investigate whether the addition of oxaliplatin to neoadjuvant chemoradiotherapy and adjuvant chemotherapy comprising capecitabine improves disease-free survival in patients with locally advanced rectal cancer. Secondary * Compare the overall survival of patients with locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy and adjuvant chemotherapy comprising capecitabine with versus without oxaliplatin. * Determine the loco-regional failure and distant failure of patients treated with these regimens. * Determine the pathological down-staging (ypT0-2N0) of patients treated with these regimens. * Determine the pathological complete remission (yp T0N0) rate of patients treated with these regimens. * Determine the tumor progression grade and histopathological R0 resection of patients treated with these regimens. * Determine the sphincter preservation rate of patients treated with these regimens. * Determine the perioperative complication rate of these regimens in these patients. * Determine the toxicity of these regimens in these patients. OUTLINE: This is a multicenter study. Patients are stratified according to treating center, clinical T category (T1-3 vs T4), clinical nodal status (Nx vs NO vs N1-2), distance from the tumor to the anal verge (≤ 5 cm vs \> 5 cm) and method of locoregional staging (EUS+MRI vs EUS+CTscan vs MRI alone). Patients are randomized to 1 of 2 treatment arms. * Arm I (control): * Neoadjuvant therapy: Patients receive oral capecitabine twice daily on days 1-35. Patients also undergo concurrent 3-dimensional conformal radiotherapy 5 days a week on days 1-33 followed by surgery. Patients may receive additional chemoradiotherapy on days 36-38. * Adjuvant therapy: Beginning 4-8 weeks after surgery, patients receive oral capecitabine twice daily on days 1-15. Treatment repeats every 3 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. * Arm II (investigational): * Neoadjuvant therapy: Patients receive oral capecitabine twice daily and undergo concurrent 3-dimensional conformal radiotherapy 5 days a week on days 1-33. Patients also receive oxaliplatin IV over 1 hour on days 1, 8, 15, 22, and 29 prior to radiotherapy followed by surgery. Patients may receive additional chemoradiotherapy on days 36-38. * Adjuvant therapy: Beginning 4-8 weeks after surgery, patients receive oxaliplatin IV over 2 hours on day 1 and oral capecitabine twice daily on days 1-15. Treatment repeats every 3 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. After completion of study therapy, patients are followed every 3 months for 3 years, and then every 6 months for 2 years.