Adjuvant Hepatic Arterial Infusional Chemotherapy After Curative Resection of Hepatocellular Carcinoma

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Yonsei University
ClinicalTrials.gov Identifier:
NCT01088581
First received: March 16, 2010
Last updated: January 31, 2012
Last verified: January 2012
  Purpose

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.


Condition Intervention Phase
Hepatocellular Carcinoma
Drug: Adjuvant group
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Adjuvant Hepatic Arterial Infusional Chemotherapy With 5-fluorouracil and Cisplatin After Curative Resection of Hepatocellular Carcinoma: A Prospective Randomized Study

Resource links provided by NLM:


Further study details as provided by Yonsei University:

Primary Outcome Measures:
  • 2-year recurrence rate and adverse events [ Time Frame: 2-year ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • overall survival [ Time Frame: 2-year ] [ Designated as safety issue: No ]

Enrollment: 101
Study Start Date: January 2006
Study Completion Date: December 2008
Primary Completion Date: December 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
No Intervention: Observation group
No adjuvant chemotherapy after resection
Active Comparator: Adjuvant group
Adjuvant chemotherapy after resection
Drug: Adjuvant group
Adjuvant chemotherapy (5FU and cisplatin) after resection
Other Name: Adjuvant chemotherapy after 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.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01088581

Locations
Korea, Republic of
Severance Hospital
Seoul, Korea, Republic of, 120-752
Sponsors and Collaborators
Yonsei University
Investigators
Study Director: Seung Up Kim, MD Yonsei University
  More Information

No publications provided

Responsible Party: Yonsei University
ClinicalTrials.gov Identifier: NCT01088581     History of Changes
Other Study ID Numbers: 4-2005-0203
Study First Received: March 16, 2010
Last Updated: January 31, 2012
Health Authority: Korea: Food and Drug Administration

Keywords provided by Yonsei University:
hepatocellular carcinoma
hepatic arterial infusion chemotherapy
5-fluorouracil
cisplatin
adjuvant chemotherapy
hepatectomy

Additional relevant MeSH terms:
Carcinoma, Hepatocellular
Carcinoma
Adenocarcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Cisplatin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents

ClinicalTrials.gov processed this record on October 01, 2014