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

Fecha de inicio: 1 de octubre de 1998

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 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