RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. PURPOSE: Randomized phase II trial to study the effectiveness of combination chemotherapy in treating patients who have advanced or metastatic colorectal cancer.

OBJECTIVES: I. Compare the efficacy of different schedules of irinotecan in combination with capecitabine as first-line therapy, in terms of objective response rate, in patients with advanced or metastatic colorectal cancer. II. Compare the time to treatment failure, time to progression, and overall survival of patients treated with these regimens. III. Compare the safety profile, in terms of toxicity, of these regimens in these patients. IV. Determine the quality of life in patients treated with these regimens.

PROTOCOL OUTLINE: This is a randomized, multicenter study. Patients are stratified according to performance status (0 vs 1); disease symptoms, including pain, weight loss, loss of appetite, malaise, and fever of unknown origin (yes vs no); weight loss during the past 6 months (more than 5% vs 5% or less); and disease-free interval (more than 6 months vs 6 months or less). Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive irinotecan IV over 1 hour on days 1, 8, 15, 22, and 29 and oral capecitabine twice daily on days 1-14 and 22-35. Arm II: Patients receive irinotecan IV over 1 hour on days 1 and 22 and oral capecitabine as in arm I. Treatment in both arms repeats every 6 weeks in the absence of disease progression or unacceptable toxicity. Quality of life is assessed at baseline, on day 1 of each course, and at the first visit after treatment failure. Patients are followed every 12 weeks for 1 year and then every 6 months thereafter.

PROJECTED ACCRUAL: A total of 28-74 patients (14-37 per treatment arm) will be accrued for this study.

Ages Eligible for Study:  18 Years   -   75 Years

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

Histologically or cytologically confirmed advanced or metastatic colorectal cancer

• Unresectable disease

At least 1 bidimensionally measurable lesion

• At least 2 cm in perpendicular diameters

No evidence of CNS metastases

--Prior/Concurrent Therapy--

Biologic therapy: Not specified

Chemotherapy: No prior chemotherapy for advanced or metastatic disease

Endocrine therapy: Not specified

Radiotherapy: Not specified

Surgery: At least 4 weeks since prior major surgery to the gastrointestinal tract

Other: No concurrent therapy for history of seizures or CNS disorder

--Patient Characteristics--

Age: 18 to 75

Performance status: 0-1

Life expectancy: At least 3 months

Hematopoietic:

• WBC at least 3,500/mm3
• Platelet count at least 100,000/mm3

Hepatic:

• Bilirubin normal
• SGOT/SGPT no greater than 2.5 times upper limit of normal (ULN)
• Alkaline phosphatase no greater than 2.5 times ULN

Renal: Creatinine no greater than 1.25 times ULN

Cardiovascular:

• No clinically significant cardiac disease
• No congestive heart failure
• No New York Heart Association class III or IV heart disease
• No symptomatic coronary artery disease
• No uncontrolled cardiac arrhythmia
• No myocardial infarction within the past year

Gastrointestinal:

• No evidence of dysphagia
• No malabsorption or intestinal obstruction that would affect absorption or excretion of study drugs
• No chronic diarrhea

Other:

• No other malignancy within the past 5 years except adequately treated carcinoma in situ of the cervix or localized nonmelanoma skin cancer
• No psychiatric disability that would preclude study
• No other significant medical condition
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception