Effects of sorafenib combined with low-dose interferon therapy for advanced hepatocellular carcinoma: a pilot study

• Published in: International journal of clinical oncology Vol. 21; no. 4; pp. 676 - 683
• Main Authors: Itokawa, Norio, Atsukawa, Masanori, Tsubota, Akihito, Okubo, Tomomi, Arai, Taeang, Nakagawa, Ai, Kondo, Chisa, Iwakiri, Katsuhiko
• Format: Journal Article
• Language: English
• Published: Tokyo Springer Japan 01.08.2016; Springer Nature B.V
• Subjects: Aged; Aged, 80 and over; alpha-Fetoproteins - metabolism; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biomarkers - blood; Biomarkers, Tumor - blood; Cancer Research; Cancer therapies; Carcinoma, Hepatocellular - complications; Carcinoma, Hepatocellular - drug therapy; Carcinoma, Hepatocellular - pathology; Disease Progression; Female; Hepatitis C, Chronic - complications; Hepatocyte Growth Factor - blood; Humans; Interferon-alpha - administration & dosage; Liver cancer; Liver Cirrhosis - complications; Liver Cirrhosis - virology; Liver Neoplasms - complications; Liver Neoplasms - drug therapy; Liver Neoplasms - pathology; Male; Medicine; Medicine & Public Health; Middle Aged; Niacinamide - administration & dosage; Niacinamide - analogs & derivatives; Oncology; Original Article; Phenylurea Compounds - administration & dosage; Pilot Projects; Polyethylene Glycols - administration & dosage; Protein Precursors - blood; Proteins; Prothrombin; Recombinant Proteins - administration & dosage; Studies; Surgical Oncology; Survival Rate; Vascular Endothelial Growth Factor A - blood; Hepatocellular carcinoma; α-Fetoprotein; Pegylated interferon; Vascular endothelial growth factor; Sorafenib
• ISSN: 1341-9625; 1437-7772
• DOI: 10.1007/s10147-015-0942-0

Background Sorafenib is a standard of care for advanced hepatocellular carcinoma (HCC). An in vitro study showed the synergistic effects of sorafenib and interferon for HCC. To clarify the efficacy, combination therapy with sorafenib and interferon was performed for patients with advanced HCC. Methods Pegylated interferon α-2a was administered every 2 weeks for the initial 4 weeks. Subsequently, it was combined with sorafenib. We evaluated the anti-tumor effect and biomarkers during treatment period. Results The subjects were 13 patients with advanced HCC complicated by hepatitis C virus (HCV)-related liver cirrhosis. A partial response, stable disease and progressive disease were noted in 4, 6, and 3 patients, respectively. The response rate, the disease control rate, the mean time to progression and the median survival time (MST) were 30.8 % (4/13), 76.9 % (10/13), 12.2 months, and 17.5 months, respectively. In 8 Child-Pugh class A and 5 Child-Pugh class B patients, the MST was 22.0 and 11.0 months, respectively ( p  = 0.001). In plasma vascular endothelial growth factor (VEGF), serum alpha-fetoprotein (AFP), AFP-L3, a protein induced by vitamin K absence or antagonist-II (PIVKA II), and hepatocyte growth factor (HGF), there was no pretreatment factor and no biomarker during the combination therapy to predict therapeutic effect in the present study. Conclusions The results of this study suggest that combination therapy with sorafenib and interferon could be effective and safe in advanced HCC patients with HCV-related liver cirrhosis.