介入导向下Ad-p53基因治疗晚期恶性肿瘤的临床安全性初步观察

Safety Evaluation of CT-guided Gene Therapy by Ad-p53 Artery Infusion in Patients with Advanced Malignant Tumor

目的：观察介入导向下经动脉导管系统灌注p53重组腺病毒（Ａd-p53)进行恶性肿瘤基因治疗的安全性。方法：选择经放化疗无效或复发及因故不能进行常规治疗的中晚期肿瘤患者１５例，经瘤组织主要供血动脉进行１.5×10^10-2.8±10^11pfu/次、累积剂量为９.5×10^10-1.40×10^12pfu/例的Ａd-p53基因治疗（其中５例宫颈癌病人联合化疗并观察出现的副作用。结果：临床观察发现以发热、流感样症状为主的５种不良反应，其中发热８例，流感样症状２例，胃不适、腹泻及心动过速 各１例；血常规检查发现白细胞和血小板减少各１例，血红蛋白减少２例；肝肾功能检查发现转氨酶ＣＧＴ、ＡＳＴ升高２例；治疗前后未见心电图改变（只有１例在化疗开始当天出现心动过速，第２天又恢复正常），与化疗联合治疗未产生强于单纯化疗的副作用。上述毒副反应以Ⅰ级反应为主（占８６.8%)，无Ⅲ、Ⅳ级反应。结论：在所用试剂量范围内Ａd-p53经动脉局部用药及与化疗联合治疗是安全可行的。

Objective: The current study was designed to test the safety of CT-guided gene therapy by Ad-p53 artery infusion in the patients with advanced malignant tumors. Methods: Fifteen patients with advanced malignant tumor, who had failed in chemotherapy and/or radiotherapy, or who were unable to be administered routine treatment for some special reasons, were administered artery infusion with adenovirus-mediated p53 gene at the doses ranging from 1. 5 × 1010 to 2. 8 ×10~11 pfu/dose (total dosage from 9. 5 ×10~10 to 1. 40 ×10~12 pfu/person). Among them, 5 patients with cervical carcinoma were treated in combination with chemotherapy. All patients were monitored for adverse events that would appeare in treatment procedures. Results: During the treatment period, fever was observed in 8 patients and faint flu-like symptoms in 2 cases, and gastric malaise, diarrhea, and tachycardia in 1 case; Additionally, leukocytopenia and thrombocytopenia was observed in one case in blood routine examination, decrease Of hemoglobin in blood routine examination, and amino-transferase in liver function examination was observed in 2 patients each. All side-effects were very mild except that WHO Grade Ⅱfever was observed in 3 patients. No evident ECG changes were observed in the treatment. Conclusion: Ranging the doses assessed in this study, CT-guided gene therapy by Ad-p53 artery infusion in the patients with advanced malignant tumor is safe and feasible.