Sorafenib Tosylate in Treating Patients With Liver Cancer That Can Be Removed by Surgery

DISEASE CHARACTERISTICS:

• Histologically confirmed hepatocellular carcinoma (HCC)

  • Fibrolamellar or mixed histology allowed
  • No cholangiocarcinoma or other tubal disease
• Must be eligible for conservative hepatic resection or liver resection with curative intent
• No cirrhosis with Child-Pugh score > 7
• Chronic liver disease without liver insufficiency and without portal liver hypertension allowed
• No known history or presence of metastatic brain or meningeal tumors

PATIENT CHARACTERISTICS:

• ECOG performance status 0-1
• Life expectancy ≥ 3 months
• WBC > 3,000/µL
• ANC > 1,500/µL
• Platelet count ≥ 100,000/µL
• Hemoglobin ≥ 9 g/dL
• Bilirubin < 1.5 times upper normal limit (ULN)
• AST and ALT ≤ 5 times UNL
• Alkaline phosphatase ≤ 5 times ULN
• Serum creatinine < 2 times ULN
• PT/INR/PTT < 1.5 times UNL
• Amylase and lipase < 1.5 times ULN
• Negative pregnancy test
• Fertile patients must use effective contraception
• Body mass index 18.5-30 kg/m^2 (WHO normal range: 18.5-25 kg/m^2)
• Able to swallow oral compound
• No criterion for unresectability or medical condition that contraindicates surgical resection

• No serious concurrent systemic disorder incompatible with the study, including any of the following:

  • Uncontrolled hypertension (i.e., BP > 150/100 mm Hg despite optimal therapy)
  • Active uncontrolled infection
  • Active alcoholism

• No prior medical disorder, including any of the following:

  • Cardiac arrhythmias requiring anti-arrhythmics (excluding beta-blockers or digoxin for chronic atrial fibrillation)
  • Active coronary artery disease or ischemia
  • Myocardial infarction within the past 6 months
  • NYHA class III-IV congestive heart failure
  • Pulmonary embolism within the past 6 months
  • Gastrointestinal bleeding within the past 6 months
• No other prior malignancy within the past 5 years, except basal cell or squamous cell skin carcinoma or cured in situ cervical carcinoma
• No history or concurrent seizure disorder requiring medications (e.g., antiepileptic drugs)
• No history of HIV infection, or chronic hepatitis B or C
• No active clinically serious bacterial or fungal infection (i.e., grade 2 CTCAE v. 3)
• No condition that is unstable or could jeopardize the safety of the patient and his/her compliance with the study
• No substance abuse or medical, psychological, or social condition that could interfere with adherence to the study
• No known or suspected allergy to the investigational agent or to any agent given concurrently
• No presence of asthenia or rash > CTC grade 1 at enrollment
• Must be registered in a national health-care system

PRIOR CONCURRENT THERAPY:

• No prior orthotopic liver transplantation
• Not a candidate for orthotopic liver transplantation
• No prior systemic or loco-regional treatment for HCC
• No prior organ allograft
• No treatment with any other investigational medicinal product within the past 28 days

• No concurrent treatment with full-dose anticoagulants

  • Deep-vein or catheter-associated thrombosis prophylaxis allowed
  • Warfarin or heparin therapy allowed if the coagulation parameters were within the acceptable ranges prior to initiation of anticoagulant therapy
• No concurrent or chronic co-administration of CYP3A4 inducers (e.g., rifampin, Hypericum perforatum, phenytoin, carbamazepine, phenobarbital, or dexamethasone)