Lin Xubin, Huang Huiqiang, Li Su, Li Hongli, Li Yuhong, Cao Ye, Zhang Dongsheng, Xia Yunfei, Guo Ying, Huang Wenlin, Jiang Wenqi
State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-sen University, Guangzhou, PR China.
Cancer Biol Ther. 2007 May;6(5):648-53. doi: 10.4161/cbt.6.5.4004. Epub 2007 Feb 13.
The purpose of the current study were to assess the safety and feasibility of repetitive intratumoral administration of E10A, an adenoviral vector encoding the wild-type endostatin gene, to patients with solid tumors, and to evaluate its biologic effect and the pharmacokinetics of endostatin.
Patients were treated with escalating doses from 1 x 10(10) VP to 1 x 10(12) VP of E10A intratumorally on days 1 and 8. Patients were assessed for toxicity and viral shedding, and antitumor response was evaluated by imaging techniques and tumor biopsy. Circulating levels of endostatin were examined.
Fifteen patients received 29 injections of E10A. No dose-limiting toxicity was developed, and the maximum tolerated dose had not yet been reached. Fever and local reaction of injection site were common, but rarely severe. Mild and transient hepatotoxicity was observed in one patient. Minor response of injected tumor was achieved and improvement of the control tumor was observed in one patient with nasopharyngeal carcinoma, and tumor necrosis was occurred in two patients. Sustained elevation of serum endostatin levels was detected.
Weekly intratumoral injection of up to 1 x 10(12) VP of E10A to patients with solid tumor is a feasible and well-tolerated procedure that exerts mild antitumor effects. A small and sustained elevation of endogenous endostatin in blood possibly has antitumor activity.
本研究旨在评估向实体瘤患者重复瘤内注射编码野生型内皮抑素基因的腺病毒载体E10A的安全性和可行性，并评估其生物学效应及内皮抑素的药代动力学。
患者在第1天和第8天接受瘤内注射E10A，剂量从1×10¹⁰病毒粒子（VP）逐步递增至1×10¹² VP。评估患者的毒性和病毒排泄情况，并通过成像技术和肿瘤活检评估抗肿瘤反应。检测循环中内皮抑素的水平。
15例患者接受了29次E10A注射。未出现剂量限制性毒性，尚未达到最大耐受剂量。发热和注射部位局部反应常见，但很少严重。1例患者出现轻度、短暂的肝毒性。1例鼻咽癌患者注射部位肿瘤有轻微反应，1例患者对照肿瘤有改善，2例患者出现肿瘤坏死。检测到血清内皮抑素水平持续升高。
每周向实体瘤患者瘤内注射高达1×10¹² VP的E10A是一种可行且耐受性良好的方法，具有轻度抗肿瘤作用。血液中内源性内皮抑素的小幅持续升高可能具有抗肿瘤活性。
