title: Adenovirus-mediated delivery of herpes simplex virus thymidine kinase administration improves outcome of recurrent high-grade glioma.
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).
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, P.R. China.|Beijing Key Laboratory of Brian Tumor, Beijing, P.R. China.
authors.forename: Nan
authors.initials: N
authors.lastname: Ji
authors.affiliation: Tongji Hospital Affiliated with Tongji Medical College of Huazhong University of Science and Technology, Wuhan, P.R. China.
authors.forename: Danhui
authors.initials: D
authors.lastname: Weng
authors.affiliation: Beijing Friendship Hospital, Capital Medical University, Beijing, P.R. China.
authors.forename: Cang
authors.initials: C
authors.lastname: Liu
authors.affiliation: Beijing Chao-Yang Hospital, Capital Medical University, Beijing, P.R. China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Gu
authors.affiliation: Beijing YouAn Hospital, Capital Medical University, Beijing, P.R. China.
authors.forename: Shizhang
authors.initials: S
authors.lastname: Chen
authors.affiliation: Beijing YouAn Hospital, Capital Medical University, Beijing, P.R. China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Beijing YouAn Hospital, Capital Medical University, Beijing, P.R. China.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Fan
authors.affiliation: Beijing YouAn Hospital, Capital Medical University, Beijing, P.R. China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Wang
authors.affiliation: Beijing YouAn Hospital, Capital Medical University, Beijing, P.R. China.
authors.forename: Jianfei
authors.initials: J
authors.lastname: Chen
authors.affiliation: Beijing YouAn Hospital, Capital Medical University, Beijing, P.R. China.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Tongji Hospital Affiliated with Tongji Medical College of Huazhong University of Science and Technology, Wuhan, P.R. China.
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, P.R. China.|Beijing Key Laboratory of Brian Tumor, Beijing, P.R. China.
authors.forename: Jisheng
authors.initials: J
authors.lastname: Wang
authors.affiliation: Tongji Hospital Affiliated with Tongji Medical College of Huazhong University of Science and Technology, Wuhan, P.R. China.
authors.forename: Ding
authors.initials: D
authors.lastname: Ma
authors.affiliation: Beijing YouAn Hospital, Capital Medical University, Beijing, P.R. China.
authors.forename: Ning
authors.initials: N
authors.lastname: Li
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D016022:Case-Control Studies; D003131:Combined Modality Therapy; D005260:Female; D005500:Follow-Up Studies; D015774:Ganciclovir / Q000627:therapeutic use; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000008:administration & dosage*; D005910:Glioma / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D011379:Prognosis; D015996:Survival Rate; D013937:Thymidine Kinase / Q000008:administration & dosage / Q000235:genetics*; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D013937:Thymidine Kinase; D015774:Ganciclovir
keywords: ADV-TK; gene therapy; glioblastoma; recurrent high-grade glioma