exposure to VPC and GCV will allow for tumor kill as tumor cells are 
recruited into the cycling pool. This proposal, utilizing surgical 
debulking and the repeated administration of VPC when necessary, allows 
for the treatment of all tumors, regardless of size. 
Overall Aims and Objectives: 
The study was designed to provide information on these aspects of 
this therapy: 
1. What is the short term efficacy and toxicity of a single treatment 
of pediatric malignant astrocytomas with VPC and GCV? 
2. Is efficacy further increased by the repeated treatment of these 
tumors with VPC instilled via an Ommaya reservoir? 
3 . What is the long term toxicity of treatment with VPC and GCV? 
4. Does the patient develop a systemic immune response to the VPC as 
the result of injection of murine VPC? 
Background and Significance 
1. Pediatric malignant astrocytomas: 
Brain tumors are the most common solid tumor occurring in the 
pediatric age group, averaging 2-5 cases per 100,000 per year (1). 
Astrocytomas account for about 50% of these tumors, and malignant 
astrocytomas of the supratentorial space account for about 25% of 
these (2) . Despite aggressive therapy including maximal surgical 
resection followed by adjuvant radiation therapy and/or 
chemotherapy, 5 years survival is less than 3 0% and ten year 
survival is less than 10 % (3). In addition, the pediatric brain 
does not do well after radiation therapy A significant portion of 
patients treated with this modality are significantly disabled with 
moderate to severe developmental delay (4) . When the tumors recur 
after therapy, the outcome is invariable fatal within weeks to a 
few months. 
I. Selection of Patients 
A. Inclusion Criteria 
1. Children with recurrent malignant supratentorial astrocytomas 
who have failed standard therapy for their disease will be 
eligible to enter the study. 
2. Patients will be divided into two groups based on their 
pretreatment MR scans. Patients will be divided into those 
with and without surgically resectable lesions. This decision 
will be made by the Pis in accordance with the standards of 
care of neurosurgical practice. 
3. Male or female patients from 2 to 18 years of age. Patients 
of child bearing potential must practice strict birth control 
to prevent pregnancy for the duration of the study. Men will 
be advised to use barrier protection for the duration of the 
study . 
4. Parents must possess the ability to give informed consent and 
express a willingness to meet all of the requirements of the 
protocol for the duration of the study. The patient will be 
included in the decision making process depending on age and 
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Recombinant DNA Research, Volume 18 
