TACE as an Adjuvant Therapy After Radiofrequency Ablation (RFA) for Hepatocellular Carcinoma

Inclusion Criteria:

• Aged 18 - 75 years, and refused surgery

• A solitary HCC ≤ 7.0 cm in diameter, or multiple HCC ≤ 3 lesions, each ≤ 3.0 cm indiameter

• Lesions being visible on ultrasound (US) and with an acceptable/safe path between thelesion and the skin as shown on US

• No extrahepatic metastasis

• No imaging evidence of invasion into the major portal/hepatic vein branches

• No history of encephalopathy, ascites refractory to diuretics or variceal bleeding

• A platelet count of > 40,000/mm3

• No previous treatment of HCC except liver resection

Exclusion Criteria:

• Patient compliance is poor

• The blood supply of tumor lesions is absolutely poor or arterial-venous shunt so thatTACE cannot be performed

• Previous or concurrent cancer that is distinct in primary site or histology from HCC,EXCEPT cervical carcinoma in situ, treated basal cell carcinoma, superficial bladdertumors (Ta, Tis and T1). Any cancer curatively treated > 3 years prior to entry ispermitted.

• History of cardiac disease:

• congestive heart failure > New York Heart Association (NYHA) class 2

• active coronary artery disease (myocardial infarction more than 6 months prior tostudy entry is permitted)

• cardiac arrhythmias requiring anti-arrhythmic therapy other than beta blockers,calcium channel blocker or digoxin

• uncontrolled hypertension (failure of diastolic blood pressure to fall below 90mmHg, despite the use of 3 antihypertensive drugs).

• Active clinically serious infections (> grade 2 National Cancer Institute [NCI]-CommonTerminology Criteria for Adverse Events [CTCAE] version 3.0)

• Known history of human immunodeficiency virus (HIV) infection

• Known central nervous system tumors including metastatic brain disease

• Patients with clinically significant gastrointestinal bleeding within 30 days prior tostudy entry

• Distantly extrahepatic metastasis

• History of organ allograft

• Substance abuse, medical, psychological or social conditions that may interfere withthe patient's participation in the study or evaluation of the study results

• Known or suspected allergy to the investigational agent or any agent given inassociation with this trial

• Any condition that is unstable or which could jeopardize the safety of the patient andhis/her compliance in the study

• Pregnant or breast-feeding patients. Women of childbearing potential must have anegative pregnancy test performed within seven days prior to the start of study drug.Both men and women enrolled in this trial must use adequate barrier birth controlmeasures during the course of the trial.

• Excluded therapies and medications, previous and concomitant:

• Prior use of any systemic anti-cancer treatment for HCC, eg. chemotherapy,immunotherapy or hormonal therapy (except that hormonal therapy for supportivecare is permitted). Antiviral treatment is allowed, however interferon therapymust be stopped at least 4 weeks prior to randomization.

• Prior use of systemic investigational agents for HCC

• Autologous bone marrow transplant or stem cell rescue within four months of startof study drug