Yada Masayoshi, Masumoto Akihide, Motomura Kenta, Tajiri Hirotaka, Morita Yusuke, Suzuki Hideo, Senju Takeshi, Koyanagi Toshimasa
Masayoshi Yada, Akihide Masumoto, Kenta Motomura, Hirotaka Tajiri, Yusuke Morita, Hideo Suzuki, Takeshi Senju, Toshimasa Koyanagi, Department of Hepatology, Iizuka Hospital, Iizuka, Fukuoka 820-8505, Japan.
World J Gastroenterol. 2014 Sep 21;20(35):12581-7. doi: 10.3748/wjg.v20.i35.12581.
To determine significant indicators for the efficacy of sorafenib in patients with advanced hepatocellular carcinoma (HCC).
A total of 46 patients with Barcelona Clinic Liver Cancer stage C who received sorafenib for more than 30 d at the Iizuka Hospital from June 2009 to December 2012 were enrolled in this study. Multivariate and univariate analyses were performed to evaluate the associations of hepatic function according to Child-Pugh grade, location and size of the largest tumor and adverse events of sorafenib treatment, such as hand-foot syndrome (HFS), hypertension, diarrhea, and alopecia, with the efficacy of treatment, as measured by overall survival (OS) and time to progression (TTP).
Patients included 39 men and 7 women whose ages ranged from 48 to 85 years (70.6 ± 9.6 years). HCC was classified according to etiology as follows: hepatitis C virus (n = 26), hepatitis B virus (n = 9), and other (n = 11). Liver function in patients was categorized as Child-Pugh grade A (n = 30) or B (n = 16). Tumors were categorized by size [< 5 cm (n = 33) or >5 cm (n = 13)] and the location of the largest tumor was used to categorize patients with intrahepatic (n = 28) or extrahepatic (n = 18) HCC. HFS, hypertension, diarrhea, and alopecia were present in 22 (47.8%), 19 (41.3%), 15 (32.6%) and 7 patients (15.2%), respectively. The median OS of all patients was 373 d and the median TTP was 112 d. The etiology of HCC did not correlate with the median OS and TPP. The median OS of patients with tumors < 5 cm was significantly longer than those with larger tumors (496 vs 245 d; HR = 0.19, 95%CI: 0.07-0.48; P < 0.01). According to the results of a multivariate analysis, the size of the largest tumor affected OS (HR = 0.22, 95%CI: 0.08-0.59; P < 0.01). The median TTP was significantly longer in patients with extrahepatic compared to intrahepatic major HCC (224 vs 98 d; HR = 0.32; 95%CI: 0.14-0.67; P < 0.01). The median TTP of patients with HFS was significantly longer than those without it (195 d vs 83 d; HR = 0.41, 95%CI: 0.20-0.82; P < 0.05), and the median TTP was significantly longer in patients with hypertension (195 d vs 84 d; HR = 0.43, 95%CI: 0.21-0.84; P < 0.05). According to the results of the multivariate analysis, extrahepatic major HCC (HR = 0.36, P < 0.01) and HFS (HR = 0.44, P < 0.05) prolonged TTP.
Extrahepatic major HCC and HFS are associated with prolonged TTP and are useful indicators for judging the efficacy of sorafenib treatment.
确定索拉非尼治疗晚期肝细胞癌（HCC）疗效的显著指标。
本研究纳入了2009年6月至2012年12月期间在饭冢医院接受索拉非尼治疗超过30天的46例巴塞罗那临床肝癌C期患者。进行多因素和单因素分析，以评估根据Child-Pugh分级的肝功能、最大肿瘤的位置和大小以及索拉非尼治疗的不良事件，如手足综合征（HFS）、高血压、腹泻和脱发，与以总生存期（OS）和疾病进展时间（TTP）衡量的治疗疗效之间的关联。
患者包括39名男性和7名女性，年龄范围为48至85岁（70.6±9.6岁）。HCC根据病因分类如下：丙型肝炎病毒（n = 26）、乙型肝炎病毒（n = 9）和其他（n = 11）。患者的肝功能分为Child-Pugh A级（n = 30）或B级（n = 16）。肿瘤按大小分类[<5 cm（n = 33）或>5 cm（n = 13）]，并根据最大肿瘤的位置将患者分为肝内HCC（n = 28）或肝外HCC（n = 18）。HFS、高血压、腹泻和脱发分别出现在22例（47.8%）、19例（41.3%）、15例（32.6%）和7例（15.2%）患者中。所有患者的中位OS为373天，中位TTP为112天。HCC的病因与中位OS和TPP无关。肿瘤<5 cm的患者的中位OS显著长于肿瘤较大的患者（496天对245天；HR = 0.19，95%CI：0.07 - 0.48；P < 0.01）。根据多因素分析结果，最大肿瘤的大小影响OS（HR = 0.22，95%CI：0.08 - 0.59；P < 0.01）。与肝内主要HCC相比，肝外主要HCC患者的中位TTP显著更长（224天对98天；HR = 0.32；95%CI：0.14 - 0.67；P < 0.01）。有HFS的患者的中位TTP显著长于无HFS的患者（195天对83天；HR = 0.41，95%CI：0.20 - 0.82；P < 0.05），有高血压的患者的中位TTP也显著更长（195天对84天；HR = 0.43，95%CI：0.21 - 0.84；P < 0.05）。根据多因素分析结果，肝外主要HCC（HR = 0.36，P < 0.01）和HFS（HR = 0.44，P < 0.05）可延长TTP。
肝外主要HCC和HFS与TTP延长相关，是判断索拉非尼治疗疗效的有用指标。
