title: Phase Ib trial of mutant herpes simplex virus G207 inoculated pre-and post-tumor resection for recurrent GBM.
abstract: We have previously demonstrated safety of G207, a doubly mutated (deletion of both gamma(1)34.5 loci, insertional inactivation of U(L)39) herpes simplex virus (HSV) for patients stereotactically inoculated in enhancing portions of recurrent malignant gliomas. We have now determined safety of two inoculations of G207, before and after tumor resection. Inclusion criteria were histologically proven recurrent malignant glioma, Karnofsky score >or=70, and ability to resect the tumor without ventricular system breach. Patients received two doses of G207 totaling 1.15 x 10(9) plaque-forming units with 13% of this total injected via a catheter placed stereotactically in the tumor. Two or five days later, tumor was resected en bloc with catheter in place. The balance of G207 dose was injected into brain surrounding the resection cavity. Six patients with recurrent glioblastoma multiforme were enrolled. Two days after the second G207 inoculation, one patient experienced transient fever, delirium, and hemiparesis, which entirely resolved on high-dose dexamethasone. No patient developed HSV encephalitis or required treatment with acyclovir. Radiographic and neuropathologic evidence suggestive of antitumor activity is reported. Evidence of viral replication was demonstrated. G207 appears safe for multiple dose delivery, including direct inoculation into the brain surrounding tumor resection cavity.
authors.affiliation: Department of Surgery, Division of Neurosurgery, University of Alabama at Birmingham, Birmingham, Alabama 35294-3410, USA. markert@uab.edu
authors.forename: James M
authors.initials: JM
authors.lastname: Markert
authors.forename: Peter G
authors.initials: PG
authors.lastname: Liechty
authors.forename: Wenquan
authors.initials: W
authors.lastname: Wang
authors.forename: Shanna
authors.initials: S
authors.lastname: Gaston
authors.forename: Eunice
authors.initials: E
authors.lastname: Braz
authors.forename: Matthias
authors.initials: M
authors.lastname: Karrasch
authors.forename: Louis B
authors.initials: LB
authors.lastname: Nabors
authors.forename: Michael
authors.initials: M
authors.lastname: Markiewicz
authors.forename: Alfred D
authors.initials: AD
authors.lastname: Lakeman
authors.forename: Cheryl A
authors.initials: CA
authors.lastname: Palmer
authors.forename: Jacqueline N
authors.initials: JN
authors.lastname: Parker
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Whitley
authors.forename: George Y
authors.initials: GY
authors.lastname: Gillespie
mesh_terms: D000212:Acyclovir / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000914:Antibodies, Viral / Q000097:blood; D001932:Brain Neoplasms / Q000188:drug therapy / Q000628:therapy*; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy / Q000628:therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D018139:Simplexvirus / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D016896:Treatment Outcome; D014779:Virus Replication
chemical_list: D000914:Antibodies, Viral; D000212:Acyclovir