A Randomized Phase III Trial of Three Different Regimens of CPT-11 Plus 5-Fluorouracil and Leucovorin Compared to 5-Fluorouracil and Leucovorin in Patients With Advanced Adenocarcinoma of the Colon and Rectum

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Histologically or cytologically confirmed locally advanced, locally recurrent, or
metastatic colorectal adenocarcinoma not curable by surgery or radiotherapy

- Histological or cytological requirement waived in patients who developed
radiological or clinical evidence of metastatic cancer after a prior surgical
resection unless:

- More than 5 years has elapsed since primary surgery OR

- Primary cancer was stage I or II

- Site of primary lesion must be or have been confirmed endoscopically, radiologically,
or surgically to be or have been in the large bowel

- Measurable or evaluable disease

- No CNS metastases or carcinomatous meningitis

PATIENT CHARACTERISTICS:

Age:

- 18 and over

Performance status:

- ECOG 0-2

Life expectancy:

- At least 12 weeks

Hematopoietic:

- Absolute granulocyte count at least 1,500/mm^3

- Platelet count at least 100,000/mm^3

- Hemoglobin at least 9.0 g/dL (transfusion allowed)

Hepatic:

- Bilirubin no greater than 1.5 mg/dL

- AST no greater than 5 times upper limit of normal (ULN)

- Alkaline phosphatase no greater than 5 times ULN

Renal:

- Creatinine no greater than 1.5 times ULN

Cardiovascular:

- No uncontrolled hypertension

- No unstable angina

- No symptomatic congestive heart failure

- No myocardial infarction within the past 6 months

- No serious uncontrolled arrhythmia

- No New York Heart Association class III or IV cardiac disease

Pulmonary:

- No interstitial pneumonia or extensive and symptomatic interstitial fibrosis of the
lung

- No pleural effusion or ascites that cause respiratory compromise (grade 2 or worse
dyspnea)

Other:

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No active or uncontrolled infection

- No symptomatic sensory peripheral neuropathy

- No known allergy to platinum compounds

- No history of gastrointestinal bleeding unless it is determined to be acceptable by
the enrolling physician

- No other prior or concurrent malignancy within the past 3 years except nonmelanoma
skin cancer, carcinoma in situ of the uterine cervix, or other resected malignant
tumor with less than a 10% probability of tumor relapse within 3 years of diagnosis

- No medical or psychiatric conditions that would preclude study

- No colonic or small bowel disorders with uncontrolled symptoms of more than 3 loose
stools per day

- Colostomy or ileostomy allowed at investigator's discretion

PRIOR CONCURRENT THERAPY:

Biologic therapy:

- Prior adjuvant immunotherapy for resected stage II-IV disease allowed if adjuvant
therapy concluded at least 1 year before documentation of recurrent disease

- No concurrent sargramostim (GM-CSF)

Chemotherapy:

- No prior chemotherapy for advanced colorectal cancer

- No prior standard adjuvant chemotherapy for rectal cancer

- Prior adjuvant fluorouracil for resected stage II-IV disease allowed if adjuvant
therapy concluded at least 1 year before documentation of recurrent disease

Endocrine therapy:

- Not specified

Radiotherapy:

- See Disease Characteristics

- At least 4 weeks since prior major radiotherapy (e.g., chest or bone palliative
radiotherapy)

- No prior radiotherapy to more than 15% of bone marrow

- No prior standard adjuvant radiotherapy for rectal cancer

Surgery:

- See Disease Characteristics

- At least 4 weeks since prior major surgery (e.g., laparotomy) (2 weeks for minor
surgery) and recovered

- Insertion of a vascular access device not considered major or minor surgery

Other:

- No other concurrent investigational agents