High-Dose Fluorouracil With or Without Leucovorin Compared With Standard Fluorouracil Plus Leucovorin Following Surgery in Treating Patients With Stage III Colon Cancer

OBJECTIVES:

• Compare recurrence-free survival and duration of survival in patients with stage III adenocarcinoma of the colon treated with adjuvant high-dose fluorouracil with or without leucovorin calcium versus standard fluorouracil with leucovorin calcium following curative radical resection.
• Compare the safety of these regimens in this patient population.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to regional lymph node involvement (N1 (1-3 pericolic lymph nodes) vs N2 (more than 3 pericolic lymph nodes) and participating center.

Patients are randomized to one of two treatment arms.

• Arm I: Patients receive leucovorin calcium IV followed by fluorouracil IV on days 1-5. Treatment repeats every 4 weeks for 6 courses.
• Arm II: Patients receive high-dose fluorouracil IV continuously over 48 hours weekly for 8 weeks. Treatment repeats every 8 weeks for 3 courses.

OR

• Patients receive leucovorin calcium IV over 2 hours followed by fluorouracil IV continuously over 24 hours weekly for 6 weeks. Treatment repeats every 7 weeks for 3 courses.

OR

• Patients receive leucovorin calcium IV over 2 hours followed by fluorouracil IV bolus and then fluorouracil IV continuously over 22 hours on days 1 and 2. Treatment repeats every 2 weeks for 12 courses.

Patients are followed at 1 month, every 6 months for 4.5 years, and then annually thereafter until death.

PROJECTED ACCRUAL: Approximately 1,600 patients (800 per treatment arm) will be accrued for this study within 3 years.

DISEASE CHARACTERISTICS:

• Histologically confirmed stage III adenocarcinoma or mucinous adenocarcinoma of the colon
• Must have had curative radical resection within 56 days prior to study

• No local tumor therapy (i.e., polypectomy, local excision or limited intestinal resection)

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• WHO 0-1

Life expectancy:

• Not specified

Hematopoietic:

• WBC at least 3,500/mm^3
• Platelet count at least 100,000/mm^3
• Hemoglobin greater than 10.0 g/dL

Hepatic:

• Bilirubin no greater than 2.0 mg/dL

Renal:

• Creatinine no greater than 1.5 mg/dL

Cardiovascular:

• No severe coronary heart disease
• No New York Heart Association class III or IV heart failure

Other:

• No other malignancy within the past 10 years except adequately treated basal cell skin cancer or carcinoma in situ of the cervix
• No uncontrolled infection
• No other severe disease
• No known allergy to leucovorin calcium
• No known familial adenomatous polyposis, Crohn's disease, or ulcerative colitis
• No hereditary syndrome (e.g., Gardner's syndrome, Turcot's syndrome, hereditary nonpolyposis colon cancer)
• Not pregnant or nursing
• Fertile patients must use effective contraception during and for 6 months after study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• No prior chemotherapy for colon cancer

Endocrine therapy:

• Not specified

Radiotherapy:

• No prior radiotherapy for colon cancer

Surgery:

• See Disease Characteristics

Other:

• No other concurrent systemic anticancer therapy