Interferon-alpha and 5-fluorouracil combination therapy after palliative hepatic resection in patients with advanced hepatocellular carcinoma, portal venous tumor thrombus in the major trunk, and multiple nodules.
BACKGROUND
The authors reported previously the beneficial effects of interferon (IFN)-alpha/5-fluorouracil (5-FU) combination therapy for patients with advanced hepatocellular carcinoma (HCC) who have tumor thrombi in the major portal branches. In this report, the authors describe the results from IFN/5-FU chemotherapy for patients who underwent palliative hepatic resection for advanced HCC with tumor thrombus in the main trunk of the portal vein and multiple nodules in the whole liver. In addition, they evaluated the correlation between the response to such therapy and expression of IFN-alpha type 2 receptor (IFNAR2).


METHODS
From October 1999 to December 2004, 30 patients with advanced HCC, tumor thrombi in the main trunk of the portal vein, and multiple nodules in the whole liver (Vp4 and grade 3 intrahepatic metastases) were recruited for this study. They underwent palliative hepatic resection followed by at least 2 courses of IFN/5-FU. IFNAR2 expression levels were determined by immunohistochemistry.


RESULTS
No major treatment-related complications were noted. An objective response was noted in 10 patients (33.3%) and included a complete response in 6 patients (20%), a partial response in 4 patients (13.3%), no response in 1 patient (3.3%), and progressive disease in 19 patients (63.4%). IFNAR2 expression was detected in 20 of 30 patients (66.7%). There was a significant difference in overall survival between patients with positive and negative IFNAR2 expression cases (P<.0025), and a significant correlation was observed between IFNAR2 expression and response to IFN/5-FU combination therapy (P=.0199).


CONCLUSIONS
Adjunct IFN/5-FU therapy is a promising modality for patients with advanced HCC, tumor thrombi in the major trunk, and multiple nodules after palliative hepatic resection. The results from this study indicated that the response to such therapy seemed to be correlated with IFNAR2 expression.
Nagano
Hiroaki
H
Department of Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan. hnagano@surg2.med.osaka-u.ac.jp
Miyamoto
Atsushi
A
Wada
Hiroshi
H
Ota
Hideo
H
Marubashi
Shigeru
S
Takeda
Yutaka
Y
Dono
Keizo
K
Umeshita
Koji
K
Sakon
Masato
M
Monden
Morito
M
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000601:surgery*; D003131:Combined Modality Therapy; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage*; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage*; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D011169:Portal Vein; D053633:Receptor, Interferon alpha-beta / Q000032:analysis; D020246:Venous Thrombosis / Q000150:complications*
D016898:Interferon-alpha; D053633:Receptor, Interferon alpha-beta; D005472:Fluorouracil