RATIONALE: Octreotide may be effective in preventing diarrhea that is caused by treatment with irinotecan. PURPOSE: Randomized phase III trial to study the effectiveness of octreotide in preventing diarrhea in patients who are receiving irinotecan for metastatic colon cancer.

OBJECTIVES: I. Compare the incidence of grade 2-4 diarrhea after completion of irinotecan in patients with metastatic colorectal cancer treated with octreotide vs placebo. II. Compare the duration of diarrhea and need for irinotecan dose reduction/ delay and hospitalization in patients treated with these 2 regimens. III. Collect data on tumor response and 1 year survival in patients treated with these 2 regimens. IV. Determine the pharmacokinetics and interaction of irinotecan and octreotide in a subset of these patients.

PROTOCOL OUTLINE: This is a randomized, double blind, placebo controlled, multicenter study. Patients are stratified according to prior pelvic irradiation (yes vs no), age (under 70 vs 70 and over), and ECOG performance status (0 vs 1 or 2). Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive octreotide intramuscularly (IM) once. Beginning 10-14 days later, patients receive irinotecan IV over 90 minutes on day 1. Patients also receive octreotide IM on the same day as irinotecan. Arm II: Patients receive placebo IM once. Beginning 10-14 days later, patients receive irinotecan as in arm I. Patients also receive placebo IM on the same day as irinotecan. Therapy continues every 3 weeks for at least 6 courses in the absence of disease progression or unacceptable toxicity. Patients are followed every 3 months through year 1.

PROJECTED ACCRUAL: A total of 300 patients (150 per arm) will be accrued for this study.

Ages Eligible for Study:  18 Years and above

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histologically, cytologically, and/or radiographically proven metastatic colorectal cancer with disease recurrence or progression following fluorouracil (5-FU) based chemotherapy; Acceptable 5-FU based regimens include capecitabine, 5-FU-uracil, floxuridine, S-1, or eniluracil combined with 5-FU; Acceptable 5-FU modulating agents include levamisole and leucovorin calcium
• Measurable or evaluable disease
• No known brain or leptomeningeal disease except previously irradiated lesions that do not require corticosteroids and are asymptomatic

--Prior/Concurrent Therapy--

• Biologic therapy: Not specified
• Chemotherapy: See Disease Characteristics; No prior irinotecan; At least 7 days since other prior chemotherapy and recovered
• Endocrine therapy: See Disease Characteristics
• Radiotherapy: See Disease Characteristics
• Surgery: No ostomy
• Other: Greater than 1 month since prior investigational agent; No concurrent investigational agent; No concurrent phenytoin, phenobarbital, valproic acid, or other antiepileptic therapy

--Patient Characteristics--

• Age: 18 and over
• Performance status: ECOG 0-2
• Life expectancy: At least 12 weeks
• Hematopoietic: WBC at least 3,000/mm3; Granulocyte count at least 1,500/mm3 Platelet count at least 100,000/mm3; Hemoglobin at least 9 g/dL
• Hepatic: Bilirubin no greater than 2 times upper limit of normal (ULN); SGOT or SGPT no greater than 3 times ULN (no greater than 5 times ULN if liver metastases present)
• Renal: Creatinine less than 2.0 mg/dL
• Cardiovascular: No uncontrolled hypertension; No unstable angina; No congestive heart failure; No myocardial infarction within the past 6 months; No serious cardiac arrhythmia
• Pulmonary: No interstitial pneumonia or fibrosis
• Gastrointestinal: No symptomatic cholelithiasis; No gastrointestinal disease that may result in nontherapy related diarrhea
• Other: Not pregnant or nursing; Negative pregnancy test; Fertile patients must use effective contraception; No other medical or surgical disease that may result in nontherapy related diarrhea; No other severe disease that would preclude study; No mental incapacity or psychiatric illness that would preclude study; No uncontrolled diabetes mellitus; No hypersensitivity to octreotide or any of its excipients; No active or uncontrolled infection HIV negative; No active second malignancy within the past 5 years except nonmelanomatous skin cancer or cervical carcinoma in situ of the cervix