Adjuvant Hepatic Arterial Infusional Chemotherapy After Curative Resection of Hepatocellular Carcinoma

Hepatocellular Carcinoma Clinical Trial

Official title:

Adjuvant Hepatic Arterial Infusional Chemotherapy With 5-fluorouracil and Cisplatin After Curative Resection of Hepatocellular Carcinoma: A Prospective Randomized Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01088581
• Other study ID #: 4-2005-0203
• Status: Completed
• Phase: Phase 3
• First received: March 16, 2010
• Last updated: January 31, 2012
• Start date: January 2006
• Est. completion date: December 2008

Study information

• Verified date: January 2012
• Source: Yonsei University
• Contact: n/a
• Is FDA regulated: No
• Health authority: Korea: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 101
• Est. completion date: December 2008
• Est. primary completion date: December 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular
• Hepatocellular Carcinoma

Intervention

Drug:
• Adjuvant group
Adjuvant chemotherapy (5FU and cisplatin) after resection

Locations

Country	Name	City	State
Korea, Republic of	Severance Hospital	Seoul

Sponsors (1)

Lead Sponsor	Collaborator
Yonsei University

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	2-year recurrence rate and adverse events		2-year	Yes
Secondary	overall survival		2-year	No