Combination Chemotherapy Plus Bevacizumab in Treating Patients With Advanced Colorectal Cancer

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Bevacizumab may stop the growth of colorectal cancer by stopping blood flow to the tumor. PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy plus bevacizumab in treating patients who have advanced colorectal cancer.

Sex

All

Minimum age

18 Years

DISEASE CHARACTERISTICS: Histologically confirmed advanced or metastatic adenocarcinoma of the colon and rectum Surgically unresectable disease Measurable disease Disease outside the prior radiotherapy port and/or progressive disease within the previously irradiated volume

PATIENT CHARACTERISTICS: Age: 18 and over Performance status: ECOG 0-2 Life expectancy: Not specified Hematopoietic: WBC at least 3,000/mm3 Platelet count at least 100,000/mm3 No hemorrhagic events within the past 6 months Hepatic: Bilirubin normal SGOT normal INR no greater than 1.5 Renal: Creatinine no greater than 1.5 times upper limit of normal Cardiovascular: No thromboembolic events within the past 6 months Pulmonary: No evidence of pneumonia Other: No known hypersensitivity to recombinant humanized murine monoclonal antibodies No evidence of significant active infection (e.g., peritonitis or wound abscess) Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY: Biologic therapy: No concurrent sargramostim (GM-CSF) Chemotherapy: At least 12 months since prior fluorouracil-based adjuvant chemotherapy No prior adjuvant irinotecan Endocrine therapy: Not specified Radiotherapy: See Disease Characteristics At least 2 weeks since prior radiotherapy and recovered Surgery: See Disease Characteristics Other: No prior therapy for advanced disease No concurrent therapeutic anticoagulation except for low-dose coumadin for maintenance of indwelling catheters

• BACKGROUNDGiantonio BJ, Chen HX, Catalano PJ, et al.: Bowel perforation and fistula formation in colorectal cancer patients treated on Eastern Cooperative Oncology Group (ECOG) studies E2200 and E3200. [Abstract] J Clin Oncol 22 (Suppl 14): A-3017, 199s, 2004.
• BACKGROUNDGray R, Giantonio BJ, O'Dwyer PJ, et al.: The safety of adding angiogenesis inhibition into treatment for colorectal, breast, and lung cancer: the Eastern Cooperative Oncology Group's (ECOG) experience with bevacizumab (anti-VEGF). [Abstract] Proceedings of the American Society of Clinical Oncology 22: A-825, 2003.
• RESULTGiantonio BJ, Levy DE, O'dwyer PJ, Meropol NJ, Catalano PJ, Benson AB 3rd; Eastern Cooperative Oncology Group. A phase II study of high-dose bevacizumab in combination with irinotecan, 5-fluorouracil, leucovorin, as initial therapy for advanced colorectal cancer: results from the Eastern Cooperative Oncology Group study E2200. Ann Oncol. 2006 Sep;17(9):1399-403. doi: 10.1093/annonc/mdl161. Epub 2006 Jul 27. PMID 16873427
• RESULTGiantonio BJ, Levy D, O'Dwyer PJ, et al.: Bevacizumab (anti-VEGF) plus IFL (irinotecan, fluorouracil, leucovorin) as front-line therapy for advanced colorectal cancer (advCRC): results from the Eastern Cooperative Oncology Group (ECOG) Study E2200. [Abstract] Proceedings of the American Society of Clinical Oncology 22: A-1024, 2003.
• RESULTGiantonio BJ, Levy D, Catalano PJ, et al.: Incorporating angiogenesis inhibition with bevacizumab (anti-VEGF) into frontline chemotherapy with irinotecan (CPT-11), fluorouracil and leucovorin (FU/LV) for advanced colorectal cancer (advCRC): a toxicity analysis of ECOG study E2200. [Abstract] Proceedings of the American Society of Clinical Oncology 21: A-503, 2002.