Fluorouracil and Leucovorin With or Without Irinotecan in Treating Patients Following Surgery for Stage III Colorectal Cancer

OBJECTIVES:

• Compare the disease-free survival at 3 years of patients with resected stage III colorectal cancer treated with adjuvant fluorouracil and leucovorin calcium with or without irinotecan.
• Compare the disease-free and overall survival at 5 years of patients treated with these regimens.
• Compare the safety profiles of these treatment regimens in these patients.
• Compare the quality-adjusted survival of patients treated with these regimens.
• Correlate the expression of putative prognostic markers (thymidylate synthase, telomerase, topoisomerase) with disease-free and overall survival of patients treated with these regimens.

OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to participating center. Patients are randomized to 1 of 2 treatment arms.

Arm I

• Patients receive irinotecan IV over 30-90 minutes, leucovorin calcium IV over 2 hours, and fluorouracil IV over 24 hours weekly for 6 weeks. Courses repeat every 7 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.
• As an alternative schedule, patients may receive irinotecan IV over 30-90 minutes and day 1 and leucovorin calcium IV over 2 hours and fluorouracil IV over 22 hours on days 1 and 2 every 2 weeks for 6 weeks. Treatment repeats every 6 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.

Arm II

• Patients receive leucovorin calcium and fluorouracil as in arm I. Quality of life may be assessed at baseline; prior to courses 2, 3, and 4; and at 1, 3, and 6 months.

Patients are followed every 3 months for 3 years and then every 6 months for 2 years.

PROJECTED ACCRUAL: Approximately 1800 patients (900 per arm) will be accrued for this study within 24 months.

DISEASE CHARACTERISTICS:

• Histologically confirmed adenocarcinoma of the colon or intraperitoneal rectum

• Stage III
• Completely resected within the past 3-8 weeks

• No gross or microscopic evidence of residual disease after surgery
• No rectal cancer requiring total meso-rectal resection or pre- or postoperative radiotherapy
• No prior curatively resected synchronous metastasis of colorectal cancer

PATIENT CHARACTERISTICS:

Age:

• 18 to 75

Performance status:

• WHO 0-1

Life expectancy:

• Not specified

Hematopoietic:

• Absolute neutrophil count at least 2,000/mm^3
• Platelet count at least 150,000/mm^3
• Hemoglobin at least 10 g/dL

Hepatic:

• Bilirubin no greater than upper limit of normal (ULN)
• AST and ALT no greater than 2.5 times ULN
• Alkaline phosphatase no greater than 2.5 times ULN

Renal:

• Creatinine no greater than 1.5 mg/dL OR
• Creatinine clearance at least 60 mL/min

Cardiovascular:

• No myocardial infarction with the past year
• No uncontrolled hypertension
• No high-risk uncontrolled arrhythmia
• No unstable angina pectoris

Other:

• HIV negative
• No chronic diarrhea
• No current chronic inflammation or subobstruction of bowel after surgery
• No active uncontrolled infection
• No other prior or concurrent malignancy except curatively treated nonmelanoma skin cancer or carcinoma in situ of the cervix
• No psychological, social, familial, or geographical condition that would preclude follow-up
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 6 months after study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• No prior antineoplastic chemotherapy

Endocrine therapy:

• Not specified

Radiotherapy:

• See Disease Characteristics

Surgery:

• See Disease Characteristics
• No prior celioscopic resection of primary tumor

Other:

• At least 30 days since prior participation in another clinical trial with any investigational drug
• No other concurrent experimental drugs
• No other concurrent anticancer therapy