郝医生的专栏

沙利度胺联合肝动脉栓塞化疗治疗原发性肝癌随机对照研究

郝明志，林海澜，陈 强，吴 晖，余文昌，陈唐庚

【摘要】背景与目的：肝动脉栓塞化疗(transcatheter arterial chemoembolization, TACE)是治疗原发性肝癌，特别是中晚期肝癌的重要治疗手段。但是如何巩固TACE的效果，进一步提高中晚期肝癌的长期生存，是我们亟待研究与解决的重要问题。本研究旨在评价沙利度胺联合TACE治疗原发性肝癌的临床疗效，探索以介入治疗为主的中晚期肝癌的综合治疗模式。方法：以疾病进展时间、生存期为观察终点指标，采用前瞻性随机对照研究，对2004年8月至2006年8月入组的96例原发性肝癌患者随机分为治疗组和对照组，治疗组给予沙利度胺200 mg/d口服1～6个月联合TACE，对照组单纯行TACE。TACE用药选用吉西它滨0.4～1.6 g、奥沙利铂100～200 mg、氟脲嘧啶脱氧核苷 0.5～1.0 g, 栓塞剂选用碘化油、明胶海绵、无水酒精。观察沙利度胺的不良反应，同时观察患者的生存期并作预后因素分析。结果：治疗组与对照组患者的中位生存期分别为18个月(95％可信区间12～24)、13个月(95％可信区间11～15)，治疗组半年、1年、2年生存率为85.6%、66.2%、29.9%，对照组半年、1年、2年生存率为85.6%、57.2%、29.1%。治疗组与对照组中位疾病进展时间分别为181天(95％可信区间91～271)和97天(95％可信区间33～161)，两组有显著性差异（P<0.05）。剔除口服沙利度胺不足3个月的病例后，治疗组与对照组中位生存期分别为28个月(95％可信区间11～45)、13个月(95％可信区间8～18)，半年、1年、2年生存率分别为97%、75.3%、51%及84.8%、54.9%、24.6%，Kaplan-Meier生存曲线和log-rank检验结果表明，两组生存期有显著性差异（P<0.05）。严重皮疹发生率11.1％，严重嗜睡发生率6.7％。Cox回归分析表明TACE次数是本研究中肝癌患者预后的独立影响因素。结论：口服沙利度胺联合TACE较单纯栓塞化疗能明显延长患者疾病进展时间与生存期，TACE次数与预后相关。

关键词：癌，肝细胞性；化学栓塞，治疗性；沙利度胺；疾病进展时间

中图分类号：R735.7；R730.53     文献标识码：A     文章编号：1000-467X

通讯作者：郝明志

Correspondence to: Hao Ming-Zhi

Tel:86-0591－83660063－8017  

E-mail: haomzys@126.com

 Efficacy of Transcatheter Arterial Chemoembolization Combined Thalidomide on Hepatocellular Carcinoma―A Controlled Randomized Study

HAO Ming-Zhi¹, LIN Hai-Lan¹, CHEN Qiang², WU Hui², YU Wen-Chang¹, CHEN Tan-Geng¹

1.Department of Interventional Radiology, Fujian Provincial Tumor Hospital, Fuzhou, Fujian, 350014, P. R. China

2. Department of Medical Oncology, Fujian Provincial Tumor Hospital, Fuzhou, Fujian, 350014, P. R. China

[ABSTRACT] BACKGROUND & OBJECTIVE: Transcatheter arterial chemoembolization (TACE) is an important therapy for hepatocellular carcinoma ,but it was still confronted with high relapse and low long-term survival of patients. Many studies showed that a combined therapy could significantly prolong the survival of patients with hepatocellular carcinoma compared to the single treatment.This study was to evaluate the efficacy of TACE combined thalidomide on hepatocellular carcinoma (HCC). METHODS: From Aug. 2004 to Aug. 2006, 96 patients with unresectable primary HCC were randomized into combination (TACE plus thalidomide) group and TACE group. Combination group received oral administration of thalidomide (200 mg/d) for 1-6 months. Both groups were treated with 0.4-1.6 gemcitabine, 100-200 mg oxaliplation, and 0.5-1.0floxuridine as chemotherapeutic drugs, ethanol, glutin, and iodolipol as ambolic agent in TACE. The side effects of  thalidomide were observed, and time to progress and long-term survival were analyzed.  RESULTS: The median survival period was 18 months [95% confidence interval (CI), 12-24 months] in combination group and 13 months (95% CI, 11-15 months) in TACE group. The 6-month, 1-year, and 2- year survival rates were respectively 85.6%、66.2%, and 29.9% in combination group, and 85.6%、57.2%, and 29.1% in TACE group. The median time to progress was significantly longer in combination group than in TACE group [181 days (95% CI, 91-271 days) vs. 97 days (95% CI, 33-161 days), P<0.05]. Excluding the patients who took thalidomide 200 mg/d for 1-3 months, the median survival period was significantly longer in combination group than in TACE group [28 months (95%CI, 11-45 months) vs. 13 months (95% CI, 8-18 months) , P<0.05] . The 6-month, 1-year, and 2- year survival rates were respectively 97%、75.3%, and 51% in combination group, and 84.8%、54.9%, and 24.6% in TACE group. The incidence of serious rashes is 11.1% and the incidence of serious somnolency is 6.7%. Multivariate Cox Analysis showed that the times of TACE in this study is an independent prognostic factors.CONCLUSIONS: Compared with TACE, the combination of TACE and thalidomide can obviously postpone disease progress and prolong survival of HCC patients. The times of TACE are the prognostic factors for patients with HCC after TACE.

KEYWORD: Carcinoma, hepatocellular;Chemoembolization, therapeutic; Thalidomide; Time to progress