TACE+RFA Versus TACE Alone for Intermediate-stage Hepatocellular Carcinoma

Transarterial Chemoembolization Plus Radiofrequency Ablation Versus Transarterial Chemoembolization Alone for Intermediate-stage Hepatocellular Carcinoma

The current standard treatment for intermediate-stage HCC (BCLC stage B) is transcatheter arterial chemoembolization (TACE) alone. The combination of TACE with RFA has also reported to be an effective treatment for HCC. Some prospective studies have shown that TACE combined with RFA have better efficacy than any of them alone for early stage HCC (single tumor ≤5 cm). However, to the investigators' knowledge, there have not been any prospective studies to assess whether TACE combined sequentially with RFA is more effective than TACE alone for the treatment of intermediate-stage HCC. The investigators hypothesized that the combination of TACE and RFA might result in better patient survival than TACE alone. Thus, the purpose of this study was to prospectively compare the effects of sequential TACE-RFA with TACE alone for the treatment of intermediate-stage HCC. Intermediate-stage HCC in this study was defined as 2-3 intrahepatic lessions, largest tumor size 3-7 cm or 4-10 intrahepatic lessions, largest tumor size ≤7 cm; ECOG-PS 0; Child-pugh A or B7; no tumor thrombus or extrahepatic metastases.

Inclusion Criteria:

• Multiple HCC (2-3 lesions), largest lesion 3-7 cm in diameter, or multiple HCC (4-10 lesions), each ≤ 7 cm in diameter
• No vascular invasion or etrahepatic metastases
• Eastern Cooperative Oncology Group Performance Status 0
• Child-Pugh Stage A or B7
• Screening laboratory values must meet the following criteria and should be obtained within 14 days prior to procedure:

I.Adequate hematologic function:

1. WBC ≥ 4.0 x 109/L (stable, off any growth factor within 4 weeks of study drug administration)
2. Neutrophils ≥ 1.5 x 109/L (stable, off any growth factor within 4 weeks of study drug administration)
3. Platelets ≥ 60 x 109/L (transfusion to achieve this level is not permitted)
4. Hemoglobin ≥ 100 g/L (may be transfused to meet this requirement)

II.Adequate hepatic function:

1. Serum Aspartate Aminotransferase (AST) ≤ 5×ULN
2. Serum Alanine Aminotransferase (ALT) ≤ 5×ULN
3. Serum total bilirubin ≤ 51.3 μmol/L
4. Serum albumin ≥ 2.8 g/dL

III.Adequate coagulation function:

a)prothrombin activity ≥ 40%

IV.Adequate renal function:

a)Serum creatinine < 110 μmol/L

Exclusion Criteria:

• Previous local therapy completed less than 4 weeks prior to the dosing and, if present any related acute toxicity > grade 1
• Any contraindications for TACE/RFA procedure:

I.Impaired clotting test (platelet count < 60000/mm3, prothrombin activity < 40%) II.Renal failure / insufficiency requiring hemodialysis or peritoneal dialysis. III.Known severe atheromatosis IV.Known uncontrolled blood hypertension (> 160/100 mmHg) V.Patients with known active bleeding (e.g. from GI ulcers, esophageal varices) within 2 months prior to baseline/screening visit or with history or evidence of inherited bleeding diathesis or coagulopathy VI.Clinically significant third space fluid accumulation (i.e., ascites requiring tapping despite use of diuretic or pleural effusion that either required tapping or is associated with shortness of breath)

• Evidence of hepatic discompensation (i.e., refractory ascites, esophageal or gastric variceal bleeding, or hepatic encephalophathy)
• Patients with any other malignancies within the last 3 years before study start
• History of HCC tumor rupture
• Clinically significant (CTC grade 3 or 4) venous or arterial thrombotic disease within past 6 months
• History of abdominal fistula, GI perforation, or intra-abdominal abscess within past 6 months prior to study treatment
• Pregnant women or lactating women
• Be allergic to pirarubicin, lobaplatin and iodized oil