Adjuvant Hepatic Arterial Infusional Chemotherapy After Curative Resection of Hepatocellular Carcinoma

Sponsor

Yonsei University (Other)

Overall Status

Completed

CT.gov ID

NCT01088581

Collaborator

(none)

101

Enrollment

Location

Arms

Duration (Months)

2.9

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Hepatocellular Carcinoma	Drug: Adjuvant group	Phase 3

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

101 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, 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

Study Start Date :

Jan 1, 2006

Actual Primary Completion Date :

Dec 1, 2007

Actual Study Completion Date :

Dec 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
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 Names: Adjuvant chemotherapy after resection

Arm

Intervention/Treatment

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 Names:

Adjuvant chemotherapy after resection

Outcome Measures

Primary Outcome Measures

2-year recurrence rate and adverse events [2-year]

Secondary Outcome Measures

overall survival [2-year]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

maximum diameter of HCC ≥5 cm,
microvascular or bile duct invasion upon pathological examination,
capsular invasion of HCC upon pathological examination, 4) Edmonson-Steiner grade III or IV.