Inclusion Criteria

- Adults patients (≥ 18 years of age) with a diagnosis of HCC that is not amenable to
surgical resection or local ablative therapy

- Histological confirmed HCC or clinical/laboratory diagnosis of HCC or nodules larger
than 2cm with typical vascular features or AFP > 200

- Patient must have one lesion < 8cm or up to five lesions with total diameter < 8cm

- Quantifiable disease limited to the liver; 40% of liver must be free of tumor burden

- Patient must have at least one tumor lesion that meets both of the following
criteria:

- Lesion can be accurately measured in at least one dimension according to RECIST
criteria

- Lesion has not been previously treated with surgery, radiation therapy,
radiofrequency ablation, percutaneous ethanol or acetic acid injection, or
cryoablation.

- ECOG performance status ≤ 2

- No prior systemic chemotherapy

- At least 4 weeks since prior TACE or interferon

- Not pregnant

- No significant baseline liver dysfunction. Child-Pugh class A and B 7-8 (in abscence
of ascites)

- No significant renal impairment (creatinine clearance < 30mL/minute) or patients on
dialysis

- No current infections requiring antibiotic therapy

- Not on anticoagulation or suffering from a known bleeding disorder

- No unstable coronary artery disease or recent MI

- The following laboratory parameters

- Hemoglobin ≥ 8.5g/dL

- Total bilirubin ≤ 3.0mg/dL

- ALT and AST ≤ 5x upper limit of normal

- Serum creatinine ≤ 1.5x upper limit of normal

- INR ≤ 1.5 or a PT/PTT within normal limits

- Platelet count ≥ 50,000/uL

- Ability to understand the protocol and to agree to and sign a written informed
consent document

Exclusion Criteria:

- HCC with gross vascular invasion or extrahepatic disease

- Previous or concurrent cancer that is distinct in primary site or histology from HCC
except cervical carcinoma in situ, treated basal-cell carcinoma of the skin,
superficial bladder tumors (Ta, Tis & T1), and any cancer curatively treated > 3
years prior to entry is permitted

- Renal failure requiring dialysis

- Child-Pugh B9 or C hepatic impairment

- History of cardiac disease: NYHA class 2 congestive heart failure, active coronary
artery disease, cardiac arrhythmias requiring anti-arrhythmic therapy other than beta
blockers or digoxin, and uncontrolled hypertension. Myocardial infarction more than 6
months prior to study entry is permitted.

- Active clinically serious infections (> CTCAEv3 grade 2)

- Known history of HIV

- Known central nervous system tumors including metastatic brain disease

- History of organ allograft

- Substance abuse (current), psychological, or social conditions that may interfere
with the patient's participation in the study or evaluation of the study results.

- Allergy to the investigational agents or any agent given in association with this
trial.

- Pregnant or breast-feeding patients. Both men and women enrolled in this trial must
use adequate barrier birth control measures during the course of the trial.

- Uncontrolled hypertension defined as systolic blood pressure > 150mmHg or diastolic
blood pressure > 90mmHg

- Thrombolic or embolic events such as a cerebrovascular accident including transient
ischemic attacks within the past 6 months

- Pulmonary hemorrhage/bleeding event > CTCAE Grade 2 within 4 weeks of first dose of
study drug

- Any other hemorrhage/bleeding event > CTCAE Grade 3 within 4 weeks of first dose of
study drug

- Serious non-healing wound, ulcer, or bone fracture

- Any contraindication for doxorubicin administration:

- serum bilirubin > 3mg/dL

- WBC < 3000 cells/mm3

- neutrophil < 1500 cells/mm3

- cardiac ejection fraction < 50 percent assessed by isotopic ventriculography,
echocardiography or MRI

- MUGA scan < 40% ejection fraction

- Any contraindication for hepatic embolization procedures

Excluded therapies and medications, previous and concomitant:

- Prior use of any systemic anti-cancer chemotherapy for HCC

- Prior use of any systemic investigational agents for HCC

- Major surgery within 6 weeks of start of study drug

- Radiotherapy during study or within 3 weeks prior to start of study drug

- Use of biological response modifiers such as granulocyte colony-stimulating factor
(G-CSF)within 3 weeks prio to study entry

- Autologous bone marrow transplant or stem cell rescue within four months of study
drug initiation

- Concomitant treatment with rifampin or St. John's wort