陆吉麟 张浩 石伟 崔小红 岳增辉 王永勇 伊萌

[摘要] 目的 探討重组人5型腺病毒注射液局部瘤内注射治疗晚期肝癌的临床疗效及安全性。 方法 选择2009年1月至2013年1月来自复旦大学附属华山医院的80例晚期肝癌患者，分为对照组（n=40）和观察组（n=40），对照组患者只给予顺铂及5-氟尿嘧啶化疗，观察组患者在化疗基础上联合B超引导下经皮瘤内注射重组人5型腺病毒注射液，连续使用两个周期。比较两组患者肿瘤客观有效率、肿瘤进展时间及不良反应。 结果 观察组的客观有效率为22.50%，高于对照组的5.00%，差异有统计学意义（P<0.05）。观察组的平均肿瘤进展时间为（11.93±2.54）周，高于对照组的（8.06±2.21）周，差异有统计学意义（P<0.05）。局部瘤内注射后48 h观察组血液中IFN-γ、IL-1α、IL-6及TNF-α显著高于治疗前，差异有统计学意义（P<0.05）。两组患者治疗后ALT、AST、ALP、TBIL及AFP指标均有所下降，而观察组下降幅度大于对照组，差异有统计学意义（P<0.05）。观察组患者不良反应主要为发热、局部反应及流感样症状，均为Ⅰ/Ⅱ级。观察组患者生活质量提高率为55.00%，高于对照组的22.50%，差异有统计学意义（P<0.05）。 结论 晚期肝癌患者在化疗基础上局部瘤内注射重组人5型腺病毒注射液，可提高客观有效率和患者生存期，且安全性及耐受性好。

[关键词] 肝癌;腺病毒;重组人5型腺病毒;基因疗法

[中图分类号] R738.6;R730.5          [文献标识码] A          [文章编号] 1673-9701（2021）12-0010-06

Clinical research on topical intratumoral injection of recombinant human adenovirus type 5 in the treatment of advanced liver cancer

LU Jilin1   ZHANG Hao1   SHI Wei1   CUI Xiaohong2   YUE Zenghui2   WANG Yongyong2   YI Meng3

1.Department of General Surgery， Huashan Hospital Affiliated to Fudan University， Shanghai   200050， China; 2.Department of General Surgery， Shanghai Electric Power Hospital， Shanghai 200031， China; 3.Shanghai Sunway Biotech Co.，LTD， Shanghai   200052， China

[Abstract] Objective To investigate the clinical efficacy and safety of intratumoral injection of recombinant human adenovirus type 5 in the treatment of advanced liver cancer. Methods A total of 80 patients with advanced liver cancer admitted to Huashan Hospital Affiliated to Fudan University from January 2009 to January 2013 were selected， and they were divided into the control group（n=40） and the observation group （n=40）. The patients in the control group were only treated with cisplatin and fluorouracil chemotherapy， while those in the observation group were treated with recombinant human adenovirus type 5 injection on the basis of chemotherapy combined with B-ultrasound guided percutaneous injection for two consecutive cycles. The objective efficacy rate， tumor progression time and adverse reactions （ADRs） of the two groups of tumors were compared. Results The objective efficacy rate in the observation group was 22.50%， which was higher than that of 5.00% in the control group， with statistically significant difference （P<0.05）. The tumor progression time in the observation group was （11.93±2.54） weeks， which was higher than that of （8.06±2.21） weeks in the control group，with statistically significant difference（P<0.05）. The blood levels of IFN-γ， IL-1α， IL-6 and TNF-α in the observation group 48 h after topical intratumoral injection were significantly higher than those before injection（P<0.05）. After treatment， the index levels of ALT， AST， ALP， TBIL and AFP all decreased in both groups， while the decrease in the observation group was greater than that in the control group， with statistically significant difference（P<0.05）. The main ADRs in the observation group were fever， topical reactions and influenza like symptoms， all of which were grade Ⅰ/Ⅱ. The improvement rate of quality of life in the observation group was 55.00%， which was higher than that of 22.50% in the control group，with statistically significant difference（P<0.05）. Conclusion Topical intratumoral injection of recombinant human adenovirus type 5 on the basis of chemotherapy for patients with advanced liver cancer can improve the objective efficacy rate and survival time of patients， with good safety and tolerance.

[Key words] Liver cancer; Adenovirus; Recombinant human adenovirus type 5; Gene therapy

肝癌具有极高的发病率和死亡率，是严重威胁我国人民健康的恶性疾病之一[1]。手术切除是肝癌首选的治疗手段[2]。但是，我国的肝癌患者多合并有不同程度的肝硬化，很多患者因此失去了手术机会。溶瘤腺病毒注射作为一种肿瘤的基因治疗方法日益受到关注[3-4]。重组人5型腺病毒注射液（商品名：安柯瑞）是全球第一个成功上市的溶瘤病毒药物。重组人5型腺病毒注射液是利用基因工程技术删除人5型腺病毒E1B-55kD和E3区部分基因片段而获得的一种溶瘤性腺病毒。重组人5型腺病毒注射液用于晚期肝癌治疗国内尚无报道。本院进行临床试验，分析在化疗基础上联合重组人5型腺病毒对肝癌的治疗效果，并分析其有效性和安全性，以期为临床治疗提供依据，现报道如下。……