Non-Technical Abstract 
Non-Technical Abstract 
Tumors arising in the brain are responsible for approximately 12,000 deaths annually 
in the United States. There has been little change in the outcome for adults with 
malignant brain tumors over the past few decades, despite improvements in surgical 
techniques and advances in radiation therapy. These tumors are uniformly fatal one to 
two years after diagnosis. The disease is devastating, due to its debilitating neurologic 
consequences and rapid termination in death. The patients often suffer from seizures, 
paralysis, incoordination, aphasia, confusion, memory loss, sensory deficits or visual 
loss, depending on the regions of the brain affected. In addition, they usually require 
large doses of corticosteroids early and late in their illness, and may experience 
disabling side effects of this treatment, such as edema, proximal myopathy, diabetes, 
fungal infections or deep vein thrombosis. Few patients in the older age group are able 
to work after the diagnosis. Most of the patients are incapable of self-care for several 
months before death. While there is some variation in the course of the disease with the 
type of brain tumor, no one survives glioblastomas and only a few patients are long- 
term survivors of anaplastic astrocytoma. Conventional brain tumor therapies are not 
successful because they do not distinguish tumor cells from normal cells. Creation of 
"artificial" differences in biochemical behavior of the tumor cells is an attractive 
option. This proposal seeks to make brain tumor cells sensitive to the drug ganciclovir. 
This will be achieved by directly injecting a virus which carries a gene for Herpes virus 
thymidine kinase. This gene when activated in the tumor cell will convert the relatively 
non-toxic drug ganciclovir to a toxic form and subsequently kill the tumor cell. In this 
phase I study, patients with recurrent brain tumors will receive injections of the virus 
into the bram tumor, followed by intravenous ganciclovir for 14 days. Patients eligible 
to undergo a palliative debulking procedure will receive the same treatment followed by 
resection on day 7. At the time of resection a second dose of virus will be administered 
intra-operatively into the residual, unresectable portion of the tumor, and intravenous 
ganciclovir will be continued for additional 14 days. Patients will be enrolled in groups 
of three, with each group receiving successively larger doses of adenovirus. This study 
will determine the toxicity of this therapy, provide evidence as to what portion of the 
tumor expresses the new gene, and determine the extent of virus induced injury. 
Recombinant DNA Research, Volume 20 
[349] 
