TY - JOUR
T1 - Adenovirus/herpes simplex-thymidine kinase/ganciclovir complex
T2 - Preliminary results of a phase I trial in patients with recurrent malignant gliomas
AU - Germano, Isabelle M.
AU - Fable, Jennifer
AU - Gultekin, S. Humayun
AU - Silvers, Adam
N1 - Funding Information:
Supported in part by NIH-1R03-CA-82804-01. The Authors wish to thank the members of the Data Safety Monitoring Board for their time and comments: Dr. Kalmon D. Post, MD; Jeffrey Bruce, MD; Meryl Mendelson, MD; Alberto Paciucci, MD. In addition, the Authors whish to thank Dr. Hunaldo Villalobos, Dr. Jamie Ullman, Dr. Marcia Mesenek, Dr. Ruth Abramson, Dr. Savio Woo, Dr. Seiji Kondo, Dr. Susan Margello, and Dr. Yasuko Kondo for their participation in matters pertinent to this study.
PY - 2003/12
Y1 - 2003/12
N2 - 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.
AB - 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.
KW - Adenovirus vector
KW - Anaplastic astrocytoma
KW - Gangciclovir
KW - Gene therapy
KW - Glioblastoma
KW - Thymidine kinase
UR - http://www.scopus.com/inward/record.url?scp=0346243603&partnerID=8YFLogxK
U2 - 10.1023/B:NEON.0000003657.95085.56
DO - 10.1023/B:NEON.0000003657.95085.56
M3 - Article
C2 - 14682378
AN - SCOPUS:0346243603
SN - 0167-594X
VL - 65
SP - 279
EP - 289
JO - Journal of Neuro-Oncology
JF - Journal of Neuro-Oncology
IS - 3
ER -