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胸苷激酶基因治疗恶性胶质瘤Ⅰ期临床研究
Retrovirus/herpes simplex-thymidine kinase/ganciclovir complex results of a phase Ⅰ clinical trial in patients with malignant gliomas
【摘要】 目的用插入单纯疱疹病毒胸苷激酶基因的逆转录病毒包装细胞(pLTKcSN/VPC)和更昔洛韦(Ganciclovir,GCV)治疗恶性胶质瘤,探讨其毒副作用和疗效。方法14例恶性胶质瘤尽可能切除肿瘤,瘤床多点注射pLTKcSN/VPC,注射点每人平均50点,接种量依据瘤床面积而定,每人注射量8~16ml不等,平均13.92ml/人,于术后7~10d开始,静脉点滴GCV,10mg·kg-1·d-1,分2次,12h1次,持续2周。结果本组毒性比较轻,均能耐受。胶质母细胞瘤组平均存活23.9个月,存活时间超过12个月病人占75%,存活时间超过23个月病人占50%,最长存活时间50个月的病人死于其他疾病。恶性胶质瘤组平均存活29.2个月,存活时间超过24个月病人占67%,存活时间超过36个月病人占33%,最长存活时间54个月,病人至今存活,无肿瘤复发迹象。结论pLTKcSN/VPC和GCV治疗恶性胶质瘤毒副作用低,对部分胶质瘤有比较明确的治疗作用。
【Abstract】 Objective To determine the safety and evaluate the preliminary efficacy of retroviral vecter containing the herpes simplex virus thymidine-kinase gene followed by ganciclovir treatment in adults with malignant gliomas. Methods Of the 14 patients with glioblastoma and malignant gliomas who underwent surgical resection of tumor, a mean 1.39×109 vector producing cells were injected into the brain adjacent to the tumor bed and GCV was administered 7-10 days after surgery(10 mg·kg-1·d-1)for 14 days. Results The patients who enrolled in the study did not experienced serious adverse events possibly related to the experimental therapy,despite external ventricle was opened for tumor resection in 9 cases. Median survival was 23.49 months in glioblastoma group.Seventy five percent of the patients(n=6)survived more than 12 months from the date of opration. Fifty percent of the patients(n=6)survived more than 23 months. A patient who survived 50 months died from other desease. Median survival was 29.2 months in malignant gliomas group. Sixty seven percent of the patients(n=4)survived more than 24 months. Conclusion This treatment modality is feasible and have evidence of efficacy to partial patients. Toxicity can be endured by patients.
【Key words】 Malignant glioma; Glioblastoma; Thymidine kinase gene; Therapy;
- 【文献出处】 中华神经外科杂志 ,Chinese Journal of Neurosurgery , 编辑部邮箱 ,2004年05期
- 【分类号】R739.4
- 【被引频次】9
- 【下载频次】119