【摘要】 背景及目的:具有瘤内复制能力的病毒(或称溶瘤病毒)用于治疗恶性肿瘤的研究近年来发展相当迅速,其中E1B缺失腺病毒是目前研究进展最快的溶瘤病毒之一。本研究采用自身对照的方法,观察在全身化疗的同时,部分瘤内注射E1B缺失腺病毒(H101)的近期疗效和不良反应。方法:采用多中心开放式研究。共入选50例,在全身化疗的同时,对目标病灶给予H101瘤内注射,每天1次,每次1支(0.5ml,含5×1011病毒颗粒),连续5天为1疗程。治疗期间同时联合常规化疗。记录疗效并与未注射H101的自身瘤灶对比,同时观察不良反应。结果:在可评价疗效的46例患者中,注射病灶的总有效率为30.4%,而按ITT人群分析有效率为28.0%(14/50),其中CR为3例,PR为11例;对照病灶的总有效率为13.0%,其中CR为1例,PR为5例。注射病灶的有效率明显高于对照病灶(P<0.001)。主要不良反应为注射部位局部疼痛(26.9%)和发热(30.2%),有4例出现Ⅰ级肝功能异常,1例出现Ⅱ级肝功能异常,1例出现Ⅳ级肝功能异常,4例出现Ⅳ级血液学毒性。结论:在全身化疗的同时,瘤内注射E1B缺失腺病毒(H101)对多种不同类型的恶性肿瘤具有一定疗效,其毒副作用较低,易为患者接受。更多还原

【Abstract】 BACKGROUND &OBJECTIVE:In recent years,great development have be en made in cancer therapeutics with replication-competent viruses (oncolytic viru ses), E1B deleted adenovirus is one of promising viruses. The current study was designed to evaluate the efficacy and toxicity of intratumoral H101, a E1B-dele ted adenovirus, in combination with chemotherapy on patients with cancer. METHOD S:A total of 50 patients with malignant tumors in multiple centers clinical tria l were treated with H101, 0.5ml 5×1011 viral particle per day for 5 consecutive days every three weeks. Routine chemotherapy was performed at the same time. An d the efficacy and toxicity were recorded. RESULTS:Among 46 valuable cases, the overall response rate was 30.4%. The response rate was 28.0%(14/50) among ITT population, including 3 complete response (CR) and 11 partial response (PR). The overall response rate of control lesion was 13.0%,including 1 case of CR and 5 cases of PR. Thus,the response rate in injected lesion is clearly higher than t hat in control lesion (P< 0 001). Main side effects were injection site pain (2 6.9%) and fever (30.2%). Grade 1 hepatic dysfunction was found in 4 patients, grade 2 in 1 patients, grade 4 in 1 patients. Grade 4 hematological toxicities w ere found in 4 patients. CONCLUSION:The study showed that the combination of gen etically modified adenovirus (H101) and chemotherapy possessed some effect for t reating the patients with refractory malignant tumors, and the toxicities were l ower, well tolerated.更多还原