Bevacizumab and Combination Chemotherapy as First-Line Therapy in Treating Patients With Metastatic Colorectal Cancer That Cannot Be Removed by Surgery

DISEASE CHARACTERISTICS:

• Histologically confirmed adenocarcinoma of the colon or rectum

• No other histological types

• Metastatic, unresectable disease

• No bone metastases only

• Unidimensionally measurable metastatic disease

• No CNS metastases

PATIENT CHARACTERISTICS:

• WHO performance status (PS) 0-2 OR Karnofsky PS 70-100%

• Life expectancy ≥ 12 weeks

• ANC > 1,500/mm³

• Platelet count ≥ 100,000/mm³

• Hemoglobin ≥ 10 g/dL

• Bilirubin ≤ 1.25 times normal (1.5 times normal in presence of hepatic metastases)

• AST and ALT < 3 times normal (5 times normal in presence of hepatic metastases)

• Creatinine < 1.25 times normal

• No proteinuria

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• No other cancer in the past 5 years except for carcinoma in situ of the uterine cervix or basal cell skin cancer

• No hypersensitivity to fluorouracil

• No hypersensitivity to leucovorin calcium, bevacizumab, or their excipients

• No hypersensitivity to Chinese hamster ovarian cell products or other recombinant humanized or nonhumanized monoclonal antibodies

• No allergy to irinotecan hydrochloride

• No prior reaction to attenuated vaccines (fever, jaundice)

• No poor nutritional status

• No Biermer anemia or other anemia due to vitamin B12 deficiency

• No uncontrolled symptomatic occlusion or subocclusion

• No medullary hypoplasia or severe insufficiency

• No prior chronic intestinal disease

• No Gilbert's syndrome

• No intra-abdominal inflammatory reaction (e.g., gastroduodenal ulcer, diverticulitis, or colitis)

• No chronic intestinal inflammatory disease

• No thromboembolic arterial condition in the past 6 months, including any of the following:

• Cardiovascular accident

• Transient ischemic attack

• Myocardial infarction

• No infection or serious noncancerous disease

• No condition that is unstable or would increase risk to the patient, including any of the following:

• Unstable angina

• Poorly controlled hypertension

• Severe cardiac insufficiency

• Serious arrhythmia

• Bleeding diathesis

• Pulmonary disease at risk of decompensation

• No familial, geographical, social, or psychological condition that would preclude study participation

• No prisoners or patients without guardians

PRIOR CONCURRENT THERAPY:

• At least 8 weeks since prior surgery

• At least 6 months since prior adjuvant chemotherapy

• At least 1 month since prior palliative chemotherapy

• No prior abdominal or pelvic radiotherapy

• At least 30 days since prior participation in another investigational study

• No prior bevacizumab

• No extensive intestinal resection (e.g., partial colectomy or extensive thin resection)

• No concurrent warfarin, Hypericum perforatum (St. John's wort), or prophylactic phenytoin