title: A phase 1 trial of oncolytic HSV-1, G207, given in combination with radiation for recurrent GBM demonstrates safety and radiographic responses.
abstract: G207, a mutant herpes simplex virus (HSV) type 1, is safe when inoculated into recurrent malignant glioma. 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 glioma 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.
authors.affiliation: 1] Department of Neurosurgery, University of Alabama at Birmingham, Birmingham, Alabama, USA [2] Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama, USA [3] Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: James M
authors.initials: JM
authors.lastname: Markert
authors.affiliation: School of Public Health, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Shantanu N
authors.initials: SN
authors.lastname: Razdan
authors.affiliation: Department of Medicine, Division of Preventative Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Hui-Chien
authors.initials: HC
authors.lastname: Kuo
authors.affiliation: Department of Medicine, Division of Preventative Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Alan
authors.initials: A
authors.lastname: Cantor
authors.affiliation: AK Statistics, Bavaria, Germany.
authors.forename: Anette
authors.initials: A
authors.lastname: Knoll
authors.affiliation: Institute of Medical Microbiology, University Hospital of Friedrich-Schiller-University, Jena, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Karrasch
authors.affiliation: Department of Neurology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: L Burt
authors.initials: LB
authors.lastname: Nabors
authors.affiliation: School of Public Health, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Markiewicz
authors.affiliation: Department of Neurosurgery, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Bonita S
authors.initials: BS
authors.lastname: Agee
authors.affiliation: Department of Neurosurgery, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Coleman
authors.affiliation: Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Alfred D
authors.initials: AD
authors.lastname: Lakeman
authors.affiliation: Department of Pathology, Division of Anatomic Pathology, The University of Utah, Salt Lake City, Utah, USA.
authors.forename: Cheryl A
authors.initials: CA
authors.lastname: Palmer
authors.affiliation: 1] Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama, USA [2] Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Jacqueline N
authors.initials: JN
authors.lastname: Parker
authors.affiliation: 1] Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, Alabama, USA [2] Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Whitley
authors.affiliation: Department of Radiation Oncology, University of Chicago, Chicago, Illinois, USA.
authors.forename: Ralph R
authors.initials: RR
authors.lastname: Weichselbaum
authors.affiliation: Department of Radiation Oncology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: John B
authors.initials: JB
authors.lastname: Fiveash
authors.affiliation: 1] Department of Neurosurgery, University of Alabama at Birmingham, Birmingham, Alabama, USA [2] Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, Alabama, USA [3] Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: G Yancey
authors.initials: GY
authors.lastname: Gillespie
mesh_terms: D000328:Adult; D005260:Female; D015316:Genetic Therapy; D005910:Glioma / Q000000981:diagnostic imaging / Q000235:genetics* / Q000532:radiotherapy* / Q000821:virology; D018259:Herpesvirus 1, Human / Q000235:genetics* / Q000472:pathogenicity; D006801:Humans; D008297:Male; D008875:Middle Aged; D050130:Oncolytic Virotherapy / Q000009:adverse effects; D050504:Oncolytic Viruses / Q000235:genetics / Q000472:pathogenicity; D011859:Radiography; D014779:Virus Replication / Q000235:genetics