• Compare progression-free survival (PFS) in pts. treated w/ leucovorin calcium + fluorouracil (MdG) vs leucovorin calcium + fluorouracil + oxaliplatin (OxMdG) and in pts. treated w/ capecitabine (Cap) vs capecitabine + oxaliplatin (OxCap) at 1 yr [ Designated as safety issue: No ]
  
• Compare health assessment in patients treated with MdG vs Cap and in patients treated with OxMdG vs OxCap at baseline and 14 weeks [ Designated as safety issue: No ]
  

• Compare health assessment, including quality of life, in patients treated with MdG vs OxMdG and in patients treated with Cap vs OxCap at baseline and 14 and 24 weeks [ Designated as safety issue: No ]
  
• Compare toxicity/adverse events in patients treated with MdG vs OxMdG and in patients treated with Cap vs OxCap [ Designated as safety issue: Yes ]
  
• Compare overall failure-free survival in patients treated with MdG vs OxMdG and in patients treated with Cap vs OxCap [ Designated as safety issue: No ]
  
• Compare overall survival in patients treated with MdG vs OxMdG and in patients treated with Cap vs OxCap [ Designated as safety issue: No ]
  
• Compare health economics in patients treated with MdG vs OxMdG and in patients treated with Cap vs OxCap [ Designated as safety issue: No ]
  
• Compare health assessment in patients treated with MdG vs Cap and in patients treated with OxMdG vs OxCap [ Designated as safety issue: No ]
  
• Compare toxicity/adverse events in patients treated with MdG vs Cap and in patients treated with OxMdG vs OxCap at baseline and 24 weeks [ Designated as safety issue: Yes ]
  
• Compare patients acceptability in patients treated with MdG vs Cap and in patients treated with OxMdG vs OxCap [ Designated as safety issue: No ]
  
• Compare PFS in patients treated with MdG vs Cap and in patients treated with OxMdG vs OxCap [ Designated as safety issue: No ]
  
• Compare health economics in patients treated with MdG vs Cap and in patients treated with OxMdG vs OxCap [ Designated as safety issue: No ]
  

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.