Liver Resection Versus Transarterial Chemoembolization for the Treatment of Intermediate-stage Hepatocellular Carcinoma

Sun Yat-sen University

Status and phase: Unknown; Phase 3

Conditions: Hepatocellular Carcinoma

Treatments: Drug: epirubicin , pirarubicin , hydroxycamptothecin and fluorouracil; Other: absorbable gelatin sponge particles; Procedure: liver resection; Drug: lipiodol; Procedure: transarterial chemoembolization; Drug: carboplatin

Study type: Interventional

Funder types: Other

Identifiers

NCT02755311

HCC 006

Details and patient eligibility

About

The role of transarterial chemoembolization (TACE) as the standard therapy for intermediate-stage hepatocellular carcinoma (HCC) is being challenged by increasing studies which showed that liver resection (LR) is a safe and feasible procedure with better survival outcomes than TACE does.

In light of this, the investigators have constructed a Markov model to simulate comparing LR and TACE in the treatment of intermediate-stage HCC. The results suggested that LR may provide survival benefit over TACE for the treatment of intermediate-stage HCC in cirrhotic patients. However, validating the simulated result by a study with higher quality (e.g. prospective clinical trial) would be of great value in providing a more convincing finding. Therefore, based on the established Markov model, the investigators aimed to prospectively compare the treatment efficacy and safety of LR with TACE for consecutive patients with intermediate-stage HCC.

Full description

Hepatocellular carcinoma (HCC) is the 5th most common cancer worldwide and the third most frequent cause of death of cancer. However, the management strategies for intermediate-stage HCC remain controversial without global consensus. On one hand, Barcelona Clinic Liver Cancer (BCLC) staging system recommends liver resection (LR) for very early and early-stage HCC, and transarterial chemoembolization (TACE) for intermediate-stage HCC. On the other hand, observational studies in both Eastern and Western countries have emerged to suggest that LR was safe and achieved better survival than TACE for patients with intermediate-stage HCC, but only very few studies have been conducted to directly compare LR with TACE for these patients.

In light of this, the investigators have conducted a multistate Markov model simulating a randomized clinical trial comparing LR with TACE over a follow-up period of 15 years. The results suggested that LR may provide survival benefit over TACE for the treatment of intermediate-stage HCC in cirrhotic patients. However, validating the simulated result by a study with higher quality (e.g. prospective clinical trial) would be of great value in providing a more convincing finding.Therefore, based on the established Markov model,the investigators aimed to prospectively compare the treatment efficacy and safety of LR with TACE for consecutive patients with intermediate-stage HCC.

Enrollment: 198 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• age between 18 and 75 years
• 2 to 3 lesions with at least one >3 cm in diameter; or more than 3 lesions of any diameter
• Child-Pugh A/B liver function
• no previous treatment
• an Eastern Cooperative Oncology Group performance status of 0

Exclusion criteria

• radiologic or pathological evidence of vascular invasion or extrahepatic metastases
• severe coagulopathy (prothrombin activity <40% or a platelet count of<40,000/mm3)
• evidence of hepatic decompensation including refractory ascites, esophageal or gastric variceal bleeding, or hepatic encephalopathy
• obstructive jaundice
• an American Society of Anesthesiologists score of 3 or more
• present or past history of any other concurrent malignancies
• complicated with other severe diseases such as chronic kidney disease, cardiovascular disease, auto-immunological disease, etc
• contraindications to carboplatin, epirubicin, mitomycin, or lipiodol

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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198 participants in 2 patient groups

liver resection

Experimental group

Description:

Resection was carried out under general anesthesia using a right subcostal incision with a midline extension. Intra-operative ultrasonography was performed routinely to evaluate the tumor burden, liver remnant and the possibility of a negative resection margin. The investigators performed anatomical resection aiming at a resection margin of at least 1 cm. Pringle's maneuver was routinely used with a clamp and unclamp time of 10 minutes and 5 minutes, respectively. Hemostasis of the raw liver surface was done with suturing and application of fibrin glue.

Treatment:

Procedure: liver resection

transarterial chemoembolization

Active Comparator group

Description:

A microcatheter was inserted into the feeding arteries as selectively as possible through the lobar, segmental, or subsegmental arteries, dependent on the tumor distribution and hepatic functional reserve. Hepatic artery infusion chemotherapy was performed using 300 mg carboplatin. Subsequently, chemolipiodolization was performed mixed with 5 ml of lipiodol. According to the number and size of the lesions, and liver and kidney function of the patient, the chemotherapeutic agents, including epirubicin (50-100 mg), pirarubicin (30-50 mg), hydroxycamptothecin (10-30 mg) and fluorouracil (500-1000 mg), were determined by the multidisciplinary team. If residual flow remained after infusion of these agents, additional lipiodol was injected. Embolization was performed with absorbable gelatin sponge particles 350-560 μm in diameter.

Treatment:

Drug: carboplatin

Procedure: transarterial chemoembolization

Drug: lipiodol

Other: absorbable gelatin sponge particles

Drug: epirubicin , pirarubicin , hydroxycamptothecin and fluorouracil