Combination Chemotherapy After Surgery in Treating Patients With High-Risk Stage II or Stage III Colorectal Cancer

DISEASE CHARACTERISTICS:

• Diagnosis of colorectal cancer meeting 1 of the following criteria:

  • High-risk stage IIB disease, defined as T4 disease, perforation, obstruction, < 10 nodes examined, poorly differentiated histology, extramural venous invasion, or extramural lymphatic invasion
  • Fully resected stage III disease

• Patients with rectal cancer must meet the following criteria:

  • Underwent prior total mesorectal excision surgery with negative resection (R0) margins
  • No prior pre-operative or scheduled post-operative combined chemotherapy and radiotherapy
• No evidence of residual or metastatic disease
• Deemed suitable for adjuvant chemotherapy

PATIENT CHARACTERISTICS:

• WHO performance status 0-1
• Life expectancy > 5 years with reference to noncancer-related diseases
• ANC ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• Hemoglobin ≥ 9 g/dL
• AST and ALT ≤ 2.5 times upper limit of normal
• Carcinoembryonic antigen (CEA) levels normal
• Glomerular filtration rate ≥ 30 mL/min (no moderate or severe renal impairment)
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must effective contraception

• More than 12 months since prior and no active clinically significant cardiovascular disease, including any of the following:

  • Cerebrovascular accident
  • Myocardial infarction
  • Unstable angina
  • New York Heart Association class II-IV congestive heart failure
  • Serious cardiac arrhythmia requiring medication
  • Uncontrolled hypertension (i.e., blood pressure > 150/100 mm Hg)
• Disease-free interval of ≥ 5 years for previous malignancy other than adequately treated in situ carcinoma of the uterine cervix or basal cell or squamous cell carcinoma of the skin
• No known or suspected dihydropyrimidine dehydrogenase deficiency

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• No more than 10 weeks since prior surgery and recovered
• No prior chemotherapy (except in patients randomized after 12 weeks of adjuvant therapy)
• No prior abdomino-pelvic radiotherapy, with the exception of short-course pre-operative radiotherapy for rectal cancer
• No concurrent brivudine or sorivudine for patients taking capecitabine