Adenovirus/herpes simplex-thymidine kinase/ganciclovir complex: Preliminary results of a phase I trial in patients with recurrent malignant gliomas

Isabelle M. Germano, Jennifer Fable, Sakir Gultekin, Adam Silvers

Research output: Contribution to journalArticle

106 Citations (Scopus)

Abstract

The management of patients with glioblastoma remains challenging with an average survival of 32-56 weeks. We report on a clinical trial of patients with recurrent glioblastoma treated with adenovirus/herpex simplex-thymidine kinase/ganciclovir (ADV/HSV-tk/GC). Entry criteria for this study included: recurrent malignant glioma after surgical resection and conventional radiation therapy. At the time of recurrence, computerized volumetric resection of the tumor was performed and the ADV/HSV-tk complex was injected in the tumor bed. GC was administered 24h after surgery (10 mg/kg/day) for 7 days. Patients were divided into 3 ADV/HSV-tk dose-escalating cohorts. Adenoviral vector shedding, and local or systemic toxicity did not occur in this study. Magnetic resonance imaging showed lack of increased brain edema in the treated patients. Histological examination of the 5 patients that had repeated surgery after gene therapy treatment showed lack of tissue toxicity. Additionally, PCR for HSV-tk was negative in the brain 3 months after injection. The patients' Karnofsky score was maintained ≥70 in 8/10 patients (80%) and 5/9 patients (55%) 3 and 6 months respectively, after gene therapy. Ten of 11 patients survived ≥52 weeks from diagnosis with an average survival of 112.3 weeks. One patient is still alive 248 weeks from diagnosis. These data show that the ADV/HSV-tk/GC complex at the dose used in this study is safe. Additional dose escalation is currently in progress.

Original languageEnglish (US)
Pages (from-to)279-289
Number of pages11
JournalJournal of Neuro-Oncology
Volume65
Issue number3
DOIs
StatePublished - Dec 2003
Externally publishedYes

Fingerprint

Herpes Simplex
Ganciclovir
Thymidine Kinase
Adenoviridae
Glioma
Glioblastoma
Genetic Therapy
Survival
Brain Edema
Neoplasms
Radiotherapy
Magnetic Resonance Imaging
Clinical Trials
Recurrence
Polymerase Chain Reaction

Keywords

  • Adenovirus vector
  • Anaplastic astrocytoma
  • Gangciclovir
  • Gene therapy
  • Glioblastoma
  • Thymidine kinase

ASJC Scopus subject areas

  • Clinical Neurology
  • Cancer Research
  • Oncology
  • Neuroscience(all)

Cite this

Adenovirus/herpes simplex-thymidine kinase/ganciclovir complex : Preliminary results of a phase I trial in patients with recurrent malignant gliomas. / Germano, Isabelle M.; Fable, Jennifer; Gultekin, Sakir; Silvers, Adam.

In: Journal of Neuro-Oncology, Vol. 65, No. 3, 12.2003, p. 279-289.

Research output: Contribution to journalArticle

Germano, Isabelle M. ; Fable, Jennifer ; Gultekin, Sakir ; Silvers, Adam. / Adenovirus/herpes simplex-thymidine kinase/ganciclovir complex : Preliminary results of a phase I trial in patients with recurrent malignant gliomas. In: Journal of Neuro-Oncology. 2003 ; Vol. 65, No. 3. pp. 279-289.
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