肝动脉栓塞化疗不同化疗方案治疗不可切除肝癌的前瞻性随机对照研究

Prospective Randomized Controlled Study of Transarterial Chemoembolization with Doxorubicin versus Doxorubicin/Lobaplatin/Mitomycin Combination for Unresectable Hepatocellular Carcinoma

目的：经导管动脉栓塞化疗（transcatheter arterial chemoembolization，TACE）是不可切除肝癌的首选治疗方法，但不同化疗方案对生存率的影响尚不明确，本研究旨在探讨单用盐酸表柔比星与联用洛铂、丝裂霉素方案对生存率的影响。方法：采用前瞻性随机对照方法，将肝功能良好的不可切除的大肝癌94例随机分为单药化疗组（盐酸表柔比星）、联合化疗组（联合洛铂、盐酸表柔比星、丝裂霉素），碘油化疗后使用明胶海绵阻断肿瘤供血血管。采用寿命表法计算累积生存率，Kaplan—Meier方法计算中位生存时间，Cox模型分析预后因素，并统计严重不良反应。结果：联合化疗组中位生存时间为15．9个月，3、6、9、12、15、18个月累积生存率分别为91％、79％、75％、61％、51％、31％；单药化疗组分别为5．0个月，78％、47％、35％、24％、24％、24％；两组中位生存时间（P=0．001），累计生存率（P=0．000）差异有显著性。Cox模型多因素分析提示分组及门脉癌栓为独立预后因素。严重不良反应包括急性肾衰、Ⅲ度骨髓抑制和腹腔感染，经治疗后均康复出院，无治疗相关死亡率。结论：经导管动脉化疗栓塞治疗肝功能良好、不可切除大肝癌应用盐酸表柔比星联用洛铂、丝裂霉素优于单用盐酸表柔比星组。

Objective： Transarterial chemoembolization （TACE） is recommended as the first line therapy for patients with unresectable hepatocellular carcinoma （HCC）. This study was designed to evaluate the effect of transarterial chemoembolization with Doxorubicin versus Doxorubicin/Lobaplatin/Mitomycin combination therapy on the survival of patients with unresectable hepatocellular carcinoma. Methods： A total of 94 patients with unresectable large HCC and preserved liver function were randomly assigned to be treated with Doxorubicin alone （Group A） or Doxorubicin in combination with Lobaplatin and Mitomycin （Group B）. After injection of the anticancer drug（s） mixed with lipiodol, gelfoam was injected to fully obstruct the hepatic artery. The primary objective was to increase survival and secondary objectives were improved response rate and decreased toxicity. The survival rates were obtained by Life Table method. Median survival times were obtained by Kaplan-Meier method and compared by log-rank test. The multivariate analysis was performed using Cox proportional hazards model. Results： The median and 3-, 6-, 9-, 12-, 15-, and 18-month survival rates in Group A were 15.9 months, 91%, 79%, 75%, 61%, 51%, and 31%, respectively. The median and 3-, 6-, 9-, 12-, 15-, 18-month survival rates in Group B were 5.0 months, 78%, 47%, 35%, 24%, 24%, and 24%, respectively. Multivariate analysis showed that the different regimens and portal vein embolus were independent prognostic factors. Severe toxic responses including acute renal failure, Ⅲ degree myelosuppression and abdominal infection were observed, without TACE-related death. Conclusion： Patients with unresectable large HCC and preserved liver function can be treated with TACE. A doxorubicin regimen can achieve better survival than Doxorubicin in combination with Lobaplatin and Mitomycin.