Fluorouracil and Leucovorin With or Without Irinotecan in Treating Patients With Metastatic Colorectal Cancer

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. It is not yet known whether fluorouracil and leucovorin plus irinotecan is more effective than fluorouracil and leucovorin alone for colorectal cancer. PURPOSE: Randomized phase III trial to compare the effectiveness of fluorouracil and leucovorin with or without irinotecan in treating patients who have metastatic colorectal cancer.

Sex

All

Minimum age

18 Years

DISEASE CHARACTERISTICS: Histologically proven metastatic adenocarcinoma of the colon or rectum Measurable or evaluable disease outside of any prior radiation port No CNS metastases

PATIENT CHARACTERISTICS: Age: 18 and over Performance status: WHO 0-2 Life expectancy: Not specified Hematopoietic: WBC at least 3,000/mm3 Platelet count at least 100,000/mm3 Hepatic: Bilirubin no greater than 1.25 times upper limit of normal (ULN) (1.5 times ULN if liver metastasis present) AST and ALT no greater than 3 times ULN (5 times ULN if liver metastasis present) Renal: Creatinine no greater than 1.25 times ULN Cardiovascular: No severe cardiac disease No uncontrolled angina pectoris No myocardial infarction within the past 6 months Gastrointestinal: No unresolved bowel obstruction or subobstruction No uncontrolled Crohn's disease or ulcerative colitis No history of chronic diarrhea Other: No second malignancy except carcinoma in situ of the cervix or nonmelanomatous skin cancer No other uncontrolled severe medical condition Not pregnant or nursing Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: No prior chemotherapy for metastatic disease No prior adjuvant chemotherapy containing topoisomerase I inhibitors At least 6 months since other prior adjuvant chemotherapy Endocrine therapy: Concurrent corticosteroids allowed Radiotherapy: See Disease Characteristics Surgery: Not specified Other: At least 4 weeks since other prior investigational drugs No other concurrent anticancer therapy

• RESULTKohne CH, van Cutsem E, Wils J, Bokemeyer C, El-Serafi M, Lutz MP, Lorenz M, Reichardt P, Ruckle-Lanz H, Frickhofen N, Fuchs R, Mergenthaler HG, Langenbuch T, Vanhoefer U, Rougier P, Voigtmann R, Muller L, Genicot B, Anak O, Nordlinger B; European Organisation for Research and Treatment of Cancer Gastrointestinal Group. Phase III study of weekly high-dose infusional fluorouracil plus folinic acid with or without irinotecan in patients with metastatic colorectal cancer: European Organisation for Research and Treatment of Cancer Gastrointestinal Group Study 40986. J Clin Oncol. 2005 Aug 1;23(22):4856-65. doi: 10.1200/JCO.2005.05.546. Epub 2005 Jun 6. PMID 15939923
• RESULTKohne CH, Van Custem E, Wils JA, et al.: Irinotecan improves the activity of the AIO regimen in metastatic colorectal cancer: results of EORTC GI Group study 40986. [Abstract] Proceedings of the American Society of Clinical Oncology 22: A-1018, 2003.
• RESULTKohne C, van Cutsem E, Wils J, et al.: Weekly high dose infusional 5-FU plus folinic acid (FA) with or without irinotecan (IRI) in metastatic colorectal cancer (MCRC): interim safety results of EORTC study 40986. [Abstract] Proceedings of the American Society of Clinical Oncology 21: A-532, 2002.