Leucovorin and Fluorouracil With or Without Oxaliplatin Compared to Capecitabine With or Without Oxaliplatin in Treating Patients With Metastatic Colorectal Cancer

OBJECTIVES: Primary * Compare the progression-free survival of patients with metastatic colorectal adenocarcinoma treated with leucovorin calcium and fluorouracil with vs without oxaliplatin or capecitabine with vs without oxaliplatin. * Compare the quality of life of patients treated with these fluorouracil-based vs capecitabine-based regimens. Secondary * Compare the failure-free and overall survival of patients treated with these regimens. * Compare the toxic effects and adverse events associated with these regimens in these patients. * Compare the limited health assessments of patients treated with these regimens. * Compare the health economics associated with these regimens. OUTLINE: This is a randomized, multicenter study. Patients are randomized to 1 of 4 treatment arms and receive 12 weeks of therapy. * Arm I (MdG regimen): Patients receive leucovorin calcium IV over 2 hours on day 1 and fluorouracil IV over 46 hours beginning on day 1. Treatment repeats every 14 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients with disease progression during or within 8 weeks of the completion of this regimen may cross over and receive second-line therapy on arm II. * Arm II (OxMdG regimen): Patients receive leucovorin calcium IV over 2 hours and oxaliplatin IV over 2 hours on day 1 and fluorouracil IV over 46 hours beginning on day 1. Treatment repeats every 14 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients with disease progression during or within 8 weeks of the completion of this regimen may receive second-line therapy or supportive care off-study. * Arm III (Cap regimen): Patients receive oral capecitabine twice daily on days 1-15. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Patients with disease progression during or within 8 weeks of the completion of this regimen may cross over and receive second-line therapy on arm IV. * Arm IV (OxCap regimen): Patients receive oxaliplatin IV over 2 hours on day 1 and oral capecitabine twice daily on days 1-15. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Patients with disease progression during or within 8 weeks of the completion of this regimen may receive second-line therapy or supportive care off-study. All patients are then re-evaluated at least every 6 weeks and begin another 12 weeks of therapy at any evidence (e.g., clinical, radiological, or tumor marker) of disease progression. Patients with chemo-sensitive disease may repeat alternating 12-week therapy sessions and evaluation periods indefinitely. Quality of life is assessed at baseline, at 12-14 weeks, at 24 weeks, and then every 3 months thereafter. Patients are followed every 3 months. Peer Reviewed and Funded or Endorsed by Cancer Research UK PROJECTED ACCRUAL: A total of 460 patients (115 per treatment arm) will be accrued for this study within 2 years.