A Phase 1 Trial of Oncolytic HSV-1, G207, Given in Combination With Radiation for Recurrent GBM Demonstrates Safety and Radiographic Responses
A Phase 1 Trial of Oncolytic HSV-1, G207, Given in Combination With Radiation for Recurrent GBM Demonstrates Safety and Radiographic Responses
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DOI：
10.1038/mt.2014.22
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发表时间：
2014-05-01
影响因子：
12.4
通讯作者：
Gillespie, G. Yancey
中科院分区：
文献类型：
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作者：
Markert, James M.;Razdan, Shantanu N.;Gillespie, G. Yancey
G207是一种突变型单纯疱疹病毒（HSV）1型，接种于复发性恶性胶质细胞是安全的。我们进行了一项G207的I期试验，以证明复发性恶性胶质瘤患者在单次5戈伊放射剂量前24小时进行立体定向瘤内给药的安全性。纳入了9例标准治疗后仍进行性、复发性恶性胶质瘤患者。患者接受一剂G207立体定向接种于增强肿瘤边缘的多个部位，然后接受5戈伊局部照射。治疗耐受性良好，没有患者发生HSV脑炎。初次诊断与接种G207之间的中位间隔为18个月（平均：23个月;范围：11-51个月）。9例患者中有6例至少在一个时间点病情稳定或部分缓解。发生了3例对治疗有显著放射学反应的病例。从G207接种到死亡的中位生存时间为7.5个月（95%置信区间：3.0-12.7）。总之，本研究显示了单剂量溶瘤HSV治疗加放疗治疗恶性胶质瘤患者的安全性和临床反应潜力。建议进一步研究溶瘤HSV如G207治疗人脑胶质瘤。
G207, a mutant herpes simplex virus (HSV) type 1, is safe when inoculated into recurrent malignant glionna. We conducted a phase 1 trial of G207 to demonstrate the safety of stereotactic intratumoral administration when given 24 hours prior to a single 5 Gy radiation dose in patients with recurrent malignant glioma. Nine patients with progressive, recurrent malignant glionna despite standard therapy were included. Patients received one dose of G207 stereotactically inoculated into the multiple sites of the enhancing tumor margin and were then treated focally with 5 Gy radiation. Treatment was well tolerated, and no patient developed HSV encephalitis. The median interval between initial diagnosis and G207 inoculation was 18 months (mean: 23 months; range: 11-51 months). Six of the nine patients had stable disease or partial response for at least one time point. Three instances of marked radiographic response to treatment occurred. The median survival time from G207 inoculation until death was 7.5 months (95% confidence interval: 3.0-12.7). In conclusion, this study showed the safety and the potential for clinical response of single-dose oncolytic HSV therapy augmented with radiation in the treatment of malignant glioma patients. Additional studies with oncolytic HSV such as G207 in the treatment of human glioma are recommended.