title: Treatment of hepatocellular carcinoma with major portal vein thrombosis by combined therapy with subcutaneous interferon-alpha and intra-arterial 5-fluorouracil; role of type 1 interferon receptor expression.
abstract: We previously reported the beneficial effects of combination therapy of interferon (IFN)-alpha/5-fluorouracil (FU) for advanced hepatocellular carcinoma (HCC) with tumour thrombi in the major portal branches. This report describes the results of longer follow-up and includes more than double the number of patients relative to the original report, and evaluates the role of IFN-alpha/type 2 interferon receptor (IFNAR2) expression on the response to the combination therapy. The study subjects were 55 patients with advanced HCC and tumour thrombi in the major branches of the portal vein (Vp3 or 4). They were treated with at least two courses of IFN-alpha/5-FU without major complication. In the 55 patients, 24 (43.6%) showed objective response (eight (14.5%) showed complete response, 16 (29.1%) partial response), four (7.3%) showed no response, and 27 (49.1%) showed progressive disease. Immunohistochemically, IFNAR2 expression was detected in nine out of 13 (69.2%) patients. There was significant difference in the time-to-progression survival (P = 0.0002) and the overall survival (P < 0.0001) between IFNAR2-positive and -negative cases. There was a significant correlation between IFNAR2 expression and response to IFN-alpha/5-FU combination therapy in univariate analysis (P = 0.0070). IFN-alpha/5-FU combination therapy is a promising modality for advanced HCC with tumour thrombi in the major portal branches and could significantly depend on IFNAR2 expression.
authors.affiliation: Department of Surgery and Clinical Oncology, Graduate School of Medicine, Osaka University, 2-2, Yamadaoka E-2, Suita, Osaka 565-0871, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Ota
authors.forename: H
authors.initials: H
authors.lastname: Nagano
authors.forename: M
authors.initials: M
authors.lastname: Sakon
authors.forename: H
authors.initials: H
authors.lastname: Eguchi
authors.forename: M
authors.initials: M
authors.lastname: Kondo
authors.forename: T
authors.initials: T
authors.lastname: Yamamoto
authors.forename: M
authors.initials: M
authors.lastname: Nakamura
authors.forename: B
authors.initials: B
authors.lastname: Damdinsuren
authors.forename: H
authors.initials: H
authors.lastname: Wada
authors.forename: S
authors.initials: S
authors.lastname: Marubashi
authors.forename: A
authors.initials: A
authors.lastname: Miyamoto
authors.forename: K
authors.initials: K
authors.lastname: Dono
authors.forename: K
authors.initials: K
authors.lastname: Umeshita
authors.forename: S
authors.initials: S
authors.lastname: Nakamori
authors.forename: K
authors.initials: K
authors.lastname: Wakasa
authors.forename: M
authors.initials: M
authors.lastname: Monden
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000473:pathology / Q000821:virology; D018450:Disease Progression; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D016174:Hepacivirus / Q000302:isolation & purification; D006526:Hepatitis C / Q000188:drug therapy / Q000473:pathology / Q000821:virology; D006801:Humans; D007279:Injections, Subcutaneous; D016898:Interferon-alpha / Q000008:administration & dosage; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000821:virology; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D008875:Middle Aged; D011169:Portal Vein / Q000378:metabolism / Q000473:pathology; D011379:Prognosis; D053633:Receptor, Interferon alpha-beta; D017471:Receptors, Interferon / Q000378:metabolism*; D012074:Remission Induction; D015996:Survival Rate; D013997:Time Factors; D016896:Treatment Outcome; D020246:Venous Thrombosis / Q000150:complications / Q000188:drug therapy*
chemical_list: C508033:IFNAR2 protein, human; D016898:Interferon-alpha; D008565:Membrane Proteins; D017471:Receptors, Interferon; D053633:Receptor, Interferon alpha-beta; D005472:Fluorouracil