Adjuvant Hepatic Arterial Infusional Chemotherapy After Curative Resection of Hepatocellular Carcinoma

NCT ID: NCT01088581

Last Updated: 2012-02-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 101 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-01-31
• Study Completion Date: 2008-12-31

Brief Summary

Several adjuvant therapies have been attempted to reduce uni-centric, and intra- or extrahepatic recurrence after curative surgical resection for hepatocellular carcinoma (HCC). However, because the efficacy of such adjuvant therapy remains unclear, there is no standard postoperative therapy.

The investigators investigated whether adjuvant hepatic arterial infusional chemotherapy with 5-fluorouracil (5-FU) and cisplatin reduces the recurrence of HCC after curative resection.

Detailed Description

Hepatocellular carcinoma (HCC) is one of the most common malignancies in the world. In particular, the global occurrence rate of HCC ranks first in males and fourth in females. Despite advances in diagnosis and medical, and surgical management, HCC is still considered a difficult disease to cure because of the high recurrence rate, even after surgical resection. The cumulative 3-year recurrence rate after resection with a curative aim is approximately 80%.1 Portal vein invasion and satellite nodules are important factors that predispose a patient to recurrence after resection.2 More importantly, recurrence after resection usually results in a high rate of mortality.3 Uni-centric or intrahepatic metastatic recurrence usually indicates metastatic spread from the primary tumor and is generally distinguished from multi-centric recurrence by a short interval between resection and recurrence (12 months for primary tumor spreading vs. 3 years for multi-centric recurrence).4,5 In this regard, several adjuvant therapies have been used to attempt to primarily reduce uni-centric, and intra- or extrahepatic recurrence after curative surgical resection for HCC. However, because the efficacy of adjuvant therapy after curative resection is still not clear, no recommendation for postoperative therapy exists.

Several chemotherapeutic agents, including doxorubicin, epirubicin, mitomycin C, 5-fluorouracil (5-FU), and cisplatin have been delivered into the hepatic artery via an implanted port system as the first-line regimen or adjuvant therapy after curative resection in HCC.6-8 A recent study reported that repetitive short-course hepatic arterial infusion of 5-FU and cisplatin showed significant anti-tumor effects in advanced HCC.9 With the hypothesis that post-operative chemotherapeutic agents delivered via the hepatic artery may eliminate residual cancer cells in the liver, we designed a prospective study to determine whether adjuvant hepatic arterial infusional chemotherapy (HAIC) with 5-FU and cisplatin reduced the incidence of recurrence of HCC and improved overall patient survival after curative resection.

Conditions

Hepatocellular Carcinoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Observation group

No adjuvant chemotherapy after resection

Group Type: NO_INTERVENTION

No interventions assigned to this group

Adjuvant group

Adjuvant chemotherapy after resection

Group Type: ACTIVE_COMPARATOR

Adjuvant group

Intervention Type: DRUG

Adjuvant chemotherapy (5FU and cisplatin) after resection

Interventions

Adjuvant group

Adjuvant chemotherapy (5FU and cisplatin) after resection

Intervention Type: DRUG

Other Intervention Names

Adjuvant chemotherapy after resection

Eligibility Criteria

Inclusion Criteria

• age of 18 to 70 years old
• appropriate blood test results (white blood cells (WBCs) ≥3,000/mm3, platelet count ≥50,000/mm3, total bilirubin <3mg/dl)
• a patient could enter this study if one of the following was fulfilled

1. maximum diameter of HCC ≥5 cm,

2. microvascular or bile duct invasion upon pathological examination,

3. capsular invasion of HCC upon pathological examination, 4) Edmonson-Steiner grade III or IV.

Exclusion Criteria

• patients with intra- or extrahepatic metastases at 4 weeks after resection
• Child-Pugh class B or C (n = 4)
• ECOG performance scale ≥2
• prior systemic chemotherapy, radiation, or locoregional therapy

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Yonsei University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Seung Up Kim, MD

Role: STUDY_DIRECTOR

Yonsei University

Locations

Severance Hospital

Seoul, , South Korea

Countries

South Korea

Other Identifiers

4-2005-0203

Identifier Type: -

Identifier Source: org_study_id