Sunitinib and Chemoembolization in Treating Patients With Liver Cancer That Cannot Be Removed by Surgery

DISEASE CHARACTERISTICS:

• Histologically, cytologically, or serologically* confirmed hepatocellular carcinoma meeting the following criteria:

  • 1-4 lesions
  • Involvement of 1 or both liver lobes NOTE: *Alpha-fetoprotein (AFP) > 500 mcg/L in high-risk patients

• Measurable disease by CT scan or MRI

  • Disease does not exceed 50% of the liver parenchyma
  • At least 1 lesion ≥ 3 cm in longest diameter
• Tumor burden involves < 50% of the liver

• Refused surgery OR unresectable disease due to any of the following:

  • Multifocality
  • Advanced cirrhosis
  • Comorbid illness
• Candidate for chemoembolization
• No fibrolamellar histology
• No ascites
• No known brain metastases

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2
• Life expectancy ≥ 12 weeks
• WBC ≥ 3,000/mm³
• ANC ≥ 1,500/mm³
• Hemoglobin ≥ 8.5 g/dL (transfusion allowed)
• Platelet count ≥ 100,000/mm³
• Bilirubin ≤ 2 mg/dL
• AST ≤ 5 times upper limit of normal (ULN)
• INR < 1.5
• Creatinine ≤ 2.0 mg/dL OR creatinine clearance ≥ 30 mL/min
• No bleeding diathesis or coagulopathy
• No active congestive heart failure
• No uncontrolled angina
• No myocardial infarction within the past 12 months
• No cardiac arrhythmia
• Ejection fraction ≥ 45% (in patients with known coronary artery disease and in patients > 50 years of age)
• Child-Pugh class A or B cirrhosis
• No impedance of hepatopedal blood flow (portal vein thrombosis)
• No thrombosis of the main portal vein
• No encephalopathy
• No biliary obstruction
• No variceal bleed within the past 6 months
• No history of allergic reactions attributed to compounds of similar chemical or biologic composition to sunitinib malate
• No absolute contraindication to doxorubicin, iodinated contrast material, microfibrillar collage hemostat, or dexamethasone

• No other concurrent uncontrolled illness including, but not limited to, any of the following:

  • Ongoing or active infection
  • Psychiatric illness or social situation that would limit compliance with study requirements
• No other active malignancies within the past year except nonmelanoma skin cancer or carcinoma in situ
• No significant traumatic injury within the past 4 weeks
• No QTc prolongation (i.e., QTc interval ≥ 500 msec) or other significant ECG abnormalities
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 6 months after the completion of study treatment

PRIOR CONCURRENT THERAPY:

• Recovered from prior therapy

• Prior liver-directed therapy, such as chemoembolization, radiofrequency ablation, cryoablation, or ethanol injection allowed if the following criteria are met:

  • Treated lesion remains inactive by CT scan or MRI and new lesion being embolized is distinct from the previously treated lesion
  • Radiographic progression of previously treated lesion requiring re-embolization
• Prior liver resection allowed
• Prior immunotherapy allowed
• No prior antiangiogenesis therapy

• No prior liver transplantation

  • Patients awaiting a cadaveric or orthotopic liver transplantation are eligible provided they have end-stage liver disease with a priority score of < 20 points
• More than 4 weeks since prior radiotherapy or chemotherapy (6 weeks for nitrosoureas or mitomycin C)
• More than 4 weeks since prior major surgery or open biopsy
• At least 1 week since prior fine needle biopsy
• No concurrent immunotherapy
• No concurrent radiotherapy
• No concurrent combination antiretroviral therapy for HIV-positive patients

• No concurrent therapeutic doses of coumarin-derivative anticoagulants (e.g., warfarin)

  • Doses of ≤ 1 mg/day are allowed for prophylaxis of thrombosis as long as INR ≤ 1.5
  • Both full dose and prophylactic dose low molecular weight heparin allowed as long as PT INR ≤ 1.5
• No anticipated major surgery during and for 3 months after completion of study treatment
• No other concurrent investigational agents
• No other concurrent anticancer therapy