DISEASE CHARACTERISTICS:

• Histologically confirmed colorectal adenocarcinoma

  • Primary colorectal tumor, if in situ, must be resectable with curative intent

• Unresectable metastatic disease present in liver only

  • Evaluation must be made by a specialist and multidisciplinary team (i.e., medical oncologist, hepatic surgeon, and radiologist) based on pretreatment liver MRI with liver-specific contrast (e.g., TESLA)

  • Unresectability determination criteria defined as follows:

    • Presence of > 4 metastases
    • Size of metastases > 5 cm
    • Location and distribution of metastatic disease within the liver unsuitable for resection with clear margins (e.g., involvement of both lobes of liver or invasion of intrahepatic vascular structures)
    • Extent of liver involvement precluding resection with adequate post-resection residual liver parenchyma volume for viable liver function in the immediate postoperative period
    • Inability to retain adequate vascular inflow and outflow to maintain viable liver function
    • Any liver-only metastases diagnosed synchronously with the primary tumor
• No evidence of extrahepatic metastases by CT scan of the chest, abdomen, and pelvis
• No liver metastases-only relapse within 6 months of completion of adjuvant chemotherapy after initial curative resection of primary colorectal cancer

PATIENT CHARACTERISTICS:

• WHO performance status 0-2
• Life expectancy > 3 months
• WBC > 3,000/mm³
• Platelet count > 100,000/mm³
• Neutrophil count > 1,500/mm³
• Bilirubin < 1.5 times upper limit of normal (ULN)
• Transaminases < 5 times ULN
• Creatinine < ULN OR creatinine clearance > 50 mL/min
• Adequate medical fitness to undergo neoadjuvant treatment and surgery with curative intent (hepatectomy with or without resection of primary tumour, if required)
• Negative pregnancy test
• Fertile patients must use effective contraception
• No serious, nonhealing wound, ulcer, or bone fracture
• No obvious risk (e.g., impending bowel obstruction) requiring emergency surgery after starting study treatment

• No clinically significant (i.e., active) cardiovascular disease, including any of the following:

  • Cerebrovascular accident within the past 6 months
  • Myocardial infarction within the past year
  • Uncontrolled hypertension while receiving chronic medication
  • Unstable angina
  • New York Heart Association class II-IV congestive heart failure
  • Serious cardiac arrhythmia requiring medication

• No recent active gastrointestinal inflammatory condition, such as peptic ulcer disease, diverticulitis, or inflammatory bowel disease

  • Patients with a known diagnosis of any of the above must have evidence of disease control by negative endoscopy within the past 28 days
• No evidence of bleeding diathesis or coagulopathy
• No known allergy to Chinese hamster ovary cell proteins or other recombinant human or humanized antibodies or to any excipients of bevacizumab formulation, platinum compounds, or any other components of the study drugs
• No baseline proteinuria, defined as urine protein > 1g by 24-hour urine collection

• No known peripheral neuropathy ≥ grade 1

  • Absence of deep tendon reflexes allowed if it is the sole neurological abnormality
• No known dihydropyrimidine dehydrogenase deficiency
• No contraindication to MRI (e.g., pacemakers)
• No major trauma within the past 28 days

• No pre-existing Childs Pugh ≥ grade B liver dysfunction

  • Liver biopsy to exclude significant liver disease required in patients with clinical, biochemical, or radiological findings of pre-existing liver dysfunction
• No lack of physical integrity of the upper gastrointestinal tract, malabsorption syndrome, or inability to take oral medication
• No other malignancy within the past 5 years except curatively treated basal cell skin cancer and/or carcinoma in situ of the cervix
• No psychological, familial, sociological, or geographical condition that would preclude study compliance

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• No prior therapy for metastatic colorectal cancer, including chemotherapy, targeted or experimental therapies (e.g., antivascular endothelial growth factor or antiepidermal growth factor receptor), radiotherapy to the liver, or surgery or radiofrequency ablation to liver metastases
• More than 28 days since prior major surgery or open biopsy
• More than 10 days since prior thrombolytic therapy
• At least 2 days since prior insertion of central venous access for study therapy (e.g., due to poor venous access)

• No concurrent full-dose oral anticoagulation

  • Low molecular-weight heparin allowed
• No concurrent chronic, daily high-dose acetylsalicylic acid (dose > 325 mg/day) or nonsteroidal anti-inflammatory medications (i.e., those known to inhibit platelet function at doses used to treat chronic inflammatory diseases)

• No concurrent chronic corticosteroids (dose ≥ 10 mg/day of methylprednisolone or equivalent)

  • Concurrent inhaled steroids allowed
• No concurrent dipyridamole or allopurinol
• No concurrent sorivudine or sorivudine analogues (e.g., brivudine)
• No other concurrent cytotoxic agents or investigational drugs
• No concurrent radiotherapy