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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。
BACKGROUND & OBJECTIVE: In recent years, the research on the treatment of malignant tumors with in-vivo replication ability of virus (or oncolytic virus) has developed quite rapidly. Among them, E1B-deficient adenovirus is one of the most rapidly studied oncolytic viruses. In this study, self-control method was used to observe the short-term efficacy and side effects of partial intratumoral injection of E1B-deleted adenovirus (H101) while systemic chemotherapy. METHODS: A multicenter open-label study was conducted. A total of 50 patients were enrolled in this study. Tumor was injected intraperitoneally (H101) once a day (0.5ml, containing 5 × 1011 virus particles) for 5 days for 1 course of chemotherapy. At the same time during the treatment of conventional chemotherapy. The curative effect was recorded and compared with that of the non-injected H101 tumor and the adverse reaction was observed. Results: Of the 46 evaluable patients, the total effective rate was 30.4% for the injected lesion and 28.0% (14/50) for the ITT population, with CR of 3 and PR of 11 The total effective rate of lesions was 13.0%, of which CR was 1 and PR was 5. The effective rate of injection lesions was significantly higher than the control lesions (P <0.001). The main adverse reactions were local pain (26.9%) and fever (30.2%) at the injection site. Grade Ⅰ liver dysfunction was found in 4 cases, grade Ⅱ liver dysfunction in 1 case, grade Ⅳ liver dysfunction in 1 case, and 4 cases Ⅳ hematological toxicity. Conclusions: In addition to systemic chemotherapy, intratumoral injection of E1B-deleted adenovirus (H101) has been shown to be effective in a variety of different types of malignancies with low toxicities and side effects and is readily accepted by patients.