Tomiyama Yasuyuki, Yoshioka Naoko, Yanai Yoshiaki, Kawase Tomoya, Nishina Sohji, Hara Yuichi, Yoshida Koji, Korenaga Keiko, Korenaga Masaaki, Hino Keisuke
Department of Hepatology and Pancreatology, Kawasaki Medical University, Kurashiki, Japan.
Institute of Fujisaki, Hayashibara Biochemical Lab Inc, Okayama, Japan ; Pharmaceutical Marketing Division, Otsuka Pharmaceutical Co Ltd, Tokyo, Japan.
Hepat Med. 2011 Apr 26;3:45-52. doi: 10.2147/HMER.S19695. eCollection 2011.
Type 1 interferon alpha receptor 2 (IFNAR2) in the liver has been reported to be a predictive factor for the response to intra-arterial 5-fluorouracil (5-FU) + systemic interferon (IFN)-alpha combination therapy in patients with advanced hepatocellular carcinoma. We tested whether IFNAR2 expression in peripheral blood mononuclear cells could predict the response to 5-FU + IFN.
Predictive factors for survival and response to therapy were determined in 30 patients with advanced hepatocellular carcinoma who underwent treatment with 5-FU + IFN. IFNAR2 expression in peripheral blood mononuclear cells was measured in 11 of the 30 patients.
With a mean number of 4.2 courses of combination therapy, one patient (3%) showed a complete response, eight (27%) showed partial responses, 13 (43%) had stable disease, and eight (27%) showed progressive disease. The median survival time of responders (complete response/partial response) was 12.7 months and that of nonresponders (stable disease/progressive disease) was 7.5 months. The one-year and two-year cumulative survival rates of responders and nonresponders were 87/69% and 40/11%, respectively (P = 0.019). Multivariate analysis identified response to therapy (P = 0.037) as the sole independent determinant of survival. The expression level of IFNAR2 in peripheral blood mononuclear cells was significantly (P = 0.012) higher in responders (6.5 ± 2.4) than in nonresponders (2.4 ± 0.6), even though no clinical factors were identified as being associated with the response to the combination therapy.
IFNAR2 expression in peripheral blood mononuclear cells may predict the response to 5-FU + IFN therapy in patients with advanced hepatocellular carcinoma, although these data are preliminary.
肝脏中的1型干扰素α受体2(IFNAR2)已被报道是晚期肝细胞癌患者对动脉内5-氟尿嘧啶(5-FU)+全身干扰素(IFN)-α联合治疗反应的预测因素。我们测试了外周血单个核细胞中IFNAR2的表达是否能预测对5-FU + IFN的反应。
在30例接受5-FU + IFN治疗的晚期肝细胞癌患者中确定生存和治疗反应的预测因素。在30例患者中的11例中测量外周血单个核细胞中IFNAR2的表达。
联合治疗平均疗程数为4.2个,1例患者(3%)显示完全缓解,8例(27%)显示部分缓解,13例(43%)病情稳定,8例(27%)病情进展。缓解者(完全缓解/部分缓解)的中位生存时间为12.7个月,未缓解者(病情稳定/病情进展)为7.5个月。缓解者和未缓解者的1年和2年累积生存率分别为87/69%和40/11%(P = 0.019)。多变量分析确定治疗反应(P = 0.037)是生存的唯一独立决定因素。外周血单个核细胞中IFNAR2的表达水平在缓解者(6.5±2.4)中显著高于未缓解者(2.4±0.6)(P = 0.012),尽管未发现临床因素与联合治疗反应相关。
外周血单个核细胞中IFNAR2的表达可能预测晚期肝细胞癌患者对5-FU + IFN治疗的反应,尽管这些数据是初步的。