Oncotarget

Research Papers:

Adenovirus-mediated delivery of herpes simplex virus thymidine kinase administration improves outcome of recurrent high-grade glioma

Nan Ji, Danhui Weng, Cang Liu, Zheng Gu, Shizhang Chen, Ying Guo, Zhong Fan, Xiao Wang, Jianfei Chen, Yanyan Zhao, Jianfeng Zhou, Jisheng Wang, Ding Ma and Ning Li _

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Oncotarget. 2016; 7:4369-4378. https://doi.org/10.18632/oncotarget.6737

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Abstract

Nan Ji1,6,*, Danhui Weng3,*, Cang Liu4, Zheng Gu5, Shizhang Chen2, Ying Guo2, Zhong Fan2, Xiao Wang2, Jianfei Chen2, Yanyan Zhao2, Jianfeng Zhou3, Jisheng Wang1,6, Ding Ma3, Ning Li2

1Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, P.R. China

2Beijing YouAn Hospital, Capital Medical University, Beijing, P.R. China

3Tongji Hospital Affiliated with Tongji Medical College of Huazhong University of Science and Technology, Wuhan, P.R. China

4Beijing Friendship Hospital, Capital Medical University, Beijing, P.R. China

5Beijing Chao-Yang Hospital, Capital Medical University, Beijing, P.R. China

6Beijing Key Laboratory of Brian Tumor, Beijing, P.R. China

*These authors have contributed equally to this work

Correspondence to:

Ding Ma, e-mail: dma@tjh.tjmu.edu.cn

Ning Li, e-mail: liningbjyah@vip.sina.com

Jisheng Wang, e-mail: neurowang@sina.com

Keywords: recurrent high-grade glioma, gene therapy, ADV-TK, glioblastoma

Received: September 09, 2015    Accepted: November 26, 2015    Published: December 23, 2015

ABSTRACT

Background: This randomized, open-label, multicenter, phase II clinical trial was conducted to assess the anti-tumor efficacy and safety of replication-deficient adenovirus mutant thymidine kinase (ADV-TK) in combination with ganciclovir administration in patients with recurrent high-grade glioma (HGG).

Patients and Methods: 53 patients with recurrent HGG were randomly allocated to receive intra-arterial cerebral infusion of ADV-TK or conventional treatments. The primary end point was 6-month progression-free survival (PFS-6). Secondary end points included progression-free survival (PFS), overall survival (OS), safety, and clinical benefit. This trial is registered with Clinicaltrials.gov, NCT00870181.

Results: In ADV-TK group, PFS-6 was 54.5%, the median PFS was 29.6 weeks, the median OS was 45.4 weeks, and better survivals were achieved when compared with control group. The one-year PFS and OS were 22.7% and 44.6% in ADV-TK group respectively, and clinical benefit was 68.2%. There are 2 patients alive for more than 4 years without progression in ADV-TK group. In the subgroup of glioblastoma received ADV-TK, PFS-6 was 71.4%, median PFS was 34.9 weeks, median OS was 45.7 weeks respectively, much better than those in control group. The one-year PFS and OS were 35.7% and 50.0% in ADV-TK group respectively. ADV-TK/ganciclovir gene therapy was well tolerated, and no treatment-related severe adverse events were noted.

Conclusion: Our study demonstrated a notable improvement of PFS-6, PFS and OS in ADV-TK treated group, and the efficacy and safety appear to be comparable to other reported treatments used for recurrent HGG. ADV-TK gene therapy is therefore a valuable therapeutic option for recurrent HGG.


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