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背景与目的:血管生成抑制剂在抗肿瘤新生血管生成方面显示出良好的临床应用前景,已有多个I期临床试验研究人内皮抑素重组蛋白的安全性和抗瘤活性。本试验目的是确定携带人内皮抑素基因的重组腺病毒注射液(Ad-Es)的最大耐受剂量,并推荐Ⅱ期临床试验的用量和用法。方法:设预试验组1例,1×1010病毒颗粒,单次瘤内注射。普通试验组遵循以一个自然对数级的1/2的方式递增,共14例,分三个剂量组:1×1011、5×1011、1×1012病毒颗粒/次,瘤内注射,每周1次,连续2周。结果:未观察到剂量限制性毒性,各受试者均显示出良好的耐受性。主要的不良事件为:局部反应和发热。其他不良反应有轻微的肝功能异常和流感样症状,如头痛、肌痛、乏力等。1例鼻咽癌放疗后鼻咽复发并颏下淋巴结转移的患者病情好转,12例病情稳定,2例出现进展。结论:人体对Ad-Es耐受性良好,晚期肿瘤患者使用1×1012病毒颗粒/次,瘤内注射,每周1次,连续2周,初步观察到Ad-Es的抗瘤活性。推荐Ⅱ期临床给药剂量为1.0×1012病毒颗粒/次,每周1次,连续4周。
BACKGROUND & OBJECTIVE: Angiogenesis inhibitors have shown promising clinical application in antitumor neovascularization. There are several phase I clinical trials to study the safety and antitumor activity of human endostatin recombinant protein. The objective of this study was to determine the maximum tolerated dose of a recombinant adenovirus (Ad-Es) carrying the human endostatin gene and to recommend the dosage and use of phase II clinical trials. Methods: One pre-test group, 1 × 1010 virus particles, a single intratumoral injection. The normal test group followed a logarithmic order of a natural increase of 1/2, a total of 14 cases, divided into three dose groups: 1 × 1011, 5 × 1011, 1 × 1012 virus particles / times, intratumoral injection, weekly 1 times for 2 weeks. Results: No dose-limiting toxicity was observed and each subject showed good tolerability. The main adverse events were: local reactions and fever. Other adverse reactions are mild liver dysfunction and flu-like symptoms such as headache, myalgia, fatigue and the like. One patient with nasopharyngeal recurrence and submental lymph node metastasis after radiotherapy of nasopharyngeal carcinoma got better condition, 12 patients were stable and 2 patients showed progress. Conclusion: The human body is well tolerated with Ad-Es. The advanced cancer patients were treated with 1 × 1012 virus particles per injection, intratumoral injection once a week for 2 consecutive weeks. The antitumor activity of Ad-Es was initially observed. The recommended phase II clinical dose of 1.0 × 1012 virus particles / time, once a week for 4 weeks.