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

背景与目的:肝动脉栓塞化疗(transcatheter arterial chemoembolization,TACE)是治疗中晚期肝癌的重要手段.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用药选用吉西他滨0.4～1.6 g、奥沙利铂100～200 mg、氟尿嘧啶脱氧核苷0.5～1.0 g,栓塞剂选用碘化油、明胶海绵、无水乙醇.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个月)、13个月(95%可信区间11～15个月),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天)和97天(95%可信区间33～161天),差异有统计学意义(P＜0.05).剔除口服沙利度胺不足1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个月)和13个月(95%可信区间8～18个月);治疗组半年、1年、2年生存率为97.0%、75.3%、51.0%,对照组分别为84.8%、54.9%、24.6%.Kaplan-Meier生存曲线和log-rank检验结果表明,两组生存期相比差异有统计学意义(P＜0.05).治疗组5例(11.1%)发生严重皮疹,3例(6.7%)严重嗜睡.Cox回归分析表明,TACE次数是影响肝癌预后的独立因素.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.

Efficacy of transcatheter arterial chemoembolization combined thalidomide on hepatocellular carcinoma: a controlled randomized trial

BACKGROUND & OBJECTIVE: Transcatheter arterial chemoembolization (TACE) is an important therapy for hepatocellular carcinoma (HCC), but the recurrence rate is still high and the long-term survival is unsatisfactory. This study was to evaluate the efficacy of TACE combined thalidomide on HCC. METHODS: From Aug. 2004 to Aug. 2006, 108 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 g gemcitabine, 100-200 mg oxaliplatin, and 0.5-1.0 g floxuridine as chemotherapeutic drugs, ethanol, glutin, and iodolipol as ambolic agent in TACE. The side effects of thalidomide and survival of the patients were observed. RESULTS: The median survival period was 18 months 95% confidence interval (CI), 12-24 months] in combination group and 13 months (95% CI, 10-16 months) in TACE group. The 6-month, 1-year, and 2-year survival rates were 92.9%, 82.7%, and 58.4% respectively in combination group, and 85.6%, 57.2%, and 32.3% respectively in TACE group. The median time to progression 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 for less than 1 month, the median survival period was significantly longer in combination group than in TACE group 18 months (95% CI, 12-24 months) vs. 13 months (95% CI, 10-16 months), P<0.05]? the 6-month, 1-year, and 2-year survival rates were 96.6%, 70.8%, and 44.3% respectively in combination group, and 84.7%, 54.4%, and 14.9% respectively in TACE group. The occurrence rate of serious rashes was 11.1% and that of serious somnolency was 6.7%. Multivariate Cox analysis showed that the times of TACE was an independent prognostic factor of HCC. CONCLUSIONS: Compared with TACE alone, the combination of TACE and thalidomide can obviously postpone disease progression and prolong survival of HCC patients. The times of TACE is a prognostic factor of HCC after TACE.