TACE and Adefovir Compared With Transarterial Chemoembolization (TACE) Alone for Hepatitis B Virus (HBV)-Related Unresectable Hepatocellular Carcinoma (HCC)

Tongji University

Status and phase

Unknown

Phase 2

Conditions

Hepatitis B Virus

Hepatocellular Carcinoma

Treatments

Drug: adefovir

Procedure: TACE

Study type

Interventional

Funder types

Other

Identifiers

NCT00960518

SHDSYY20090725

Details and patient eligibility

About

Hepatocellular carcinoma (HCC) is one of the most prevalent malignancies in China, and approximately 90% of the patients with HCC are also infected with hepatitis B virus (HBV). For patients with unresectable disease, the goal of palliative treatment is to control symptoms and prolong survival. Transarterial chemoembolization (TACE) using iodized oil and chemotherapeutic agents combines the effect of targeted chemotherapy with that of ischemic necrosis induced by arterial embolization. It can be administered repeatedly and can prolong survival in patients with unresectable hypervascular HCC. The long-term prognosis, however, remains guarded because of frequent development of locoregional tumor recurrence, which, together with concomitant hepatic decompensation, is the main cause of death. Adefovir works by blocking reverse transcriptase, an enzyme that is crucial for the hepatitis B virus (HBV) to reproduce in the body. Based on these results, the investigators conducted a randomized controlled trial to test the hypothesis that adefovir treatment would reduce or postpone the recurrence rate and improve the overall survival rate in patients after TACE treatment of HBV-related unresectable HCC.

Full description

Hepatocellular carcinoma (HCC) is one of the most prevalent malignancies in China, and approximately 90% of the patients with HCC are also infected with hepatitis B virus (HBV). Until now, no standard therapy has been established for treatment of hepatocellular carcinoma. For patients with unresectable disease, the goal of palliative treatment is to control symptoms and prolong survival. Transarterial chemoembolization (TACE) using iodized oil and chemotherapeutic agents combines the effect of targeted chemotherapy with that of ischemic necrosis induced by arterial embolization. It can be administered repeatedly and can prolong survival in patients with unresectable hypervascular HCC. The long-term prognosis, however, remains guarded because of frequent development of locoregional tumor recurrence, which, together with concomitant hepatic decompensation, is the main cause of death. Recurrence in the liver remnant may originate from metastasis from the primary tumor or multicentric new primaries in a cirrhotic liver.

Adefovir works by blocking reverse transcriptase, an enzyme that is crucial for the hepatitis B virus (HBV) to reproduce in the body. It is approved for the treatment of chronic hepatitis B in adults with evidence of active viral replication and either evidence of persistent elevations in serum aminotransferases (primarily ALT) or histologically active disease. The main benefit of adefovir over lamivudine (the first NRTI approved for the treatment of hepatitis B) is that it takes a much longer period of time before the virus develops resistance to it. Adefovir dipivoxil contains two pivaloyloxymethyl units, making it a prodrug form of Adefovir.

Based on these results, the investigators conducted a randomized controlled trial to test the hypothesis that adefovir treatment would reduce or postpone the recurrence rate and improve the overall survival rate in patients after TACE treatment of HBV-related unresectable HCC.

Enrollment

216 estimated patients

Sex

All

Ages

20 to 75 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

age:20-75 years old
with a clinical diagnosis of primary liver cancer, with HBsAg positive,without any therapy for tumor
single lesion with a diameter >6.5 cm,or multiple lesions locating within half liver or adjacent three lobe
estimated liver remnant volume ≤40%
with a liver function of Child-Pugh class A,and ALT≤80IU/l.

Exclusion criteria

reject to attend
portal vein trunk has been compressed by tumor
diffuse type cancer or with extensive cancer thrombus in main branches of PV,HV,IVC or bile duct
with extrahepatic metastasis
with obvious portal hypertension (with moderate to severe varix in esophagus and/or gastric fundus, enlarged spleen,WBC<4×109／L, PLT<80×109／L)
with diabetes
allergy to iodine

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

None (Open label)

216 participants in 2 patient groups, including a placebo group

TACE

Placebo Comparator group

Description:

An emulsion that consisted of 50 mg of cisplatin and 10 mL of lipiodol at a volume ratio of 1:1 was injected into the blood supply artery of the tumor under fluoroscopic guidance. The injection could be slowed or discontinued if retrograde flow occurred. Embolization was subsequently performed with granules of gelatin sponge particles.

Treatment:

Procedure: TACE

TACE+adefovir

Experimental group

Description:

patients received adefovir, at a dose of 10 mg daily after TACE treatment, for 48 weeks

Treatment:

Drug: adefovir