溶瘤腺病毒治疗实体瘤安全性及临床疗效的初步评价

Preliminary assessment on the safety and clinical efficacy of an oncolytic adenovirus to patients with solid tumors

目的探讨携带自杀基因(TK)的溶瘤腺病毒(Ad-ETK)治疗实体肿瘤患者的安全性及临床疗效。方法选择晚期实体瘤常规治疗无效或已无法实施常规治疗的患者10例,签署知情同意书后给予Ad-ETK治疗。根据不同的实体瘤Ad-ETK采用多种途径给药,包括经皮股动脉穿刺导管介入至肿瘤血管内给药4例,CT引导下瘤体局部穿刺给药4例,恶性腹水者腹腔灌注给药2例。Ad-ETK的给药剂量为(1～5)×1010pfu/次,3～6次为一个疗程。Ad-ETK给药24h后常规给予更昔洛韦0.25g/次,2次/d,静脉滴注,连续3d。治疗期间采用美国国家癌症中心制定的不良反应/事件分级(CTCAE)监测患者的不良反应,并采用实体瘤疗效评价标准(RECIST)进行临床疗效分析。结果 Ad-ETK治疗后患者最常出现的毒副反应为流感样症状,包括寒颤、发热、乏力、肌肉酸痛,毒副反应发生的程度与给药途径有关,其中以股动脉穿刺血管内给药最容易发生,其次依次为肿瘤局部注射和腹腔灌注给药。10例患者用药期间未见用药相关的心、肝、肾等重要器官的功能损害。6例患者治疗前后影像学显示实体瘤体积有不同程度的缩小,1例卵巢癌种植转移至腹腔产生大量癌性腹水的患者Ad-ETK治疗后腹水明显减少,肿瘤标记物CA125降低。结论 Ad-ETK多种途径给药均有较好的安全性,所引起的毒副反应多为轻、中度的流感样症状,患者均能耐受;此外,Ad-ETK对晚期实体瘤有一定的临床疗效。

Objective To investigate the safety and clinical efficacy of Ad-ETK,an oncolytic adenovirus encoding suicide gene (TK gene),to treat patients with solid tumors.Methods Ten patients with advanced-stage solid tumors,in whom the conventional therapies were used to be given were invalidly or lost,were rolled up in this study upon signing informed consent.According to different solid tumors,The Ad-ETK were administrated via various routes including four patients were administrated by percataneously femoral arteriopuncture to intervene into the tumor vessel,four patients were administrated by CT-guided local puncture injection,and two with malignant ascites were administrated by intraperitoneal perfusion.The doses of Ad-ETK were (1-5)×1010 pfu every time,and 3-6 times as a course of treatment.0.25 g of ganciclovir (GCV) twice a day for 3 days was intravenously administrated 24 h after given Ad-ETK.The all kinds of adverse events were monitored based on the Common Terminology Criteria for Adverse Events v3.0 (CTCAE),established by the National Cancer Institute (NCI),and the clinical efficacy of Ad-ETK was analyzed according to the Response Evaluation Criteria in Solid Tumors (RECIST).Results The common side effects after the administration of Ad-ETK was influenza-like symptoms,including rigors,fever,fatigue and muscular soreness.The frequence was associated with the route of administration,in which the side effects by percataneous femoral arteriopuncture had the most incidence,next by CT-guided percutaneously intratumoral injection and direct intraperitoneal injection,respectively.The function of important organs such as the heart,liver and kidney had no obvious damage in the period of treatment of Ad-ETK.In the ten patients,the treatment of Ad-ETK resulted in volume of tumor shrink in various degrees imaged by CT in six patients,lead to an amount of ascites significant reduction and CA125,a blood tumor marker,decrease in one with ovarian cancer accompanied by heavy malignant ascites.Conclusions Good safety of Ad-ETK is shown by the administrations of multiple routs,and common side effects have wild and mild influenza-like symptoms,of which the patients can be well tolerated.In addition,the Ad-ETK treatment made some benefit to the patients with advanced-stage solid tumors.