Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2016 Jan 26;7(4):4369-78.
doi: 10.18632/oncotarget.6737.

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

Nan Ji  1   2 , Danhui Weng  3 , Cang Liu  4 , Zheng Gu  5 , Shizhang Chen  6 , Ying Guo  6 , Zhong Fan  6 , Xiao Wang  6 , Jianfei Chen  6 , Yanyan Zhao  6 , Jianfeng Zhou  3 , Jisheng Wang  1   2 , Ding Ma  3 , Ning Li  6
Affiliations
Clinical Trial

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

Nan Ji et al. Oncotarget. .

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.

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

PubMed Disclaimer

Conflict of interest statement

CONFLICTS OF INTEREST

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1. CONSORT diagram
Figure 2
Figure 2. Kaplan-Meier plots for Progression-free Survival (PFS) and Overall Survival (OS)
A. PFS for ADV-TK group versus Control group. B. OS for ADV-TK group versus Control group.
Figure 3
Figure 3. Kaplan-Meier plots for Progression-free Survival (PFS) and Overall Survival (OS) in GBM subgroup
A. PFS for ADV-TK group versus Control group. B. OS for ADV-TK group versus Control group.
See this image and copyright information in PMC

References

    1. National Comprehensive Cancer Network. NCCN Guidelines Version 2.2011: Central Nervous System Cancers. Available at: www.nccn.org. Accessed August 16, 2011. - PubMed
    1. Phase I study of cytokine-gene modified autologous neuroblastoma cells for treatment of relapsed/refractory neuroblastoma. Human Gene Therapy. 1992;3:665–76. doi: 10.1089/hum.1992.3.6-665. - DOI - PubMed
    1. Oldfield EH, Ram Z, Culver KW, Blaese RM, DeVroom HL, Anderson WF. Gene therapy for the treatment of brain tumors using intra-tumoral transduction with the thymidine kinase gene and intravenous ganciclovir. Hum Gene Ther. 1993;4:39–69. doi: 10.1089/hum.1993.4.1-39. - DOI - PubMed
    1. Ram Z, Culver KW, Oshiro EM, Viola JJ, DeVroom HL, Otto E, Long Z, Chiang Y, McGarrity GJ, Muul LM, Katz D, Blaese RM, Oldfield EH. Therapy of malignant brain tumors by intratumoral implantation of retroviral vector-producing cells. Nat Med. 1997;3:1354–61. - PubMed
    1. Klatzmann D, Valéry CA, Bensimon G, Marro B, Boyer O, Mokhtari K, Diquet B, Salzmann JL, Philippon J. A phase I/II study of herpes simplex virus type 1 thymidine kinase “suicide” gene therapy for recurrent glioblastoma. Study Group on Gene Therapy for Glioblastoma. Hum Gene Ther. 1998;9:2595–604. doi: 10.1089/hum.1998.9.17-2595. - DOI - PubMed

Publication types

MeSH terms

Associated data