3 . 
4 . 
5. 
E. 
B. 
mg/kg/q6 hours the day of each VPC injection as indicated and 
treatment will be continued until GCV is discontinued. 
Dexamethasone will then be tapered. As experience is gained, 
the need for dexamethasone dosing may be modified. 
Mannitol : Patients may receive mannitol during the surgical 
procedure at lg/kg and the dose repeated TID for 24 hours 
following the procedure, as clinically indicated. 
Anticonvulsant : Anticonvulsive therapy will be administered 
according to the usual neurosurgical guidelines. 
Analgesics : Pain medication will include Acetaminophen 15 
mg/kg, Q 4 hours, to a maximum of 1000 mg/dose. 
The GlTkSvNa.29 Retroviral Vector (Appendix G) . GlTkSvNa.29 
is a retroviral vector derived from the Moloney murine 
leukemia virus (MoMLV) . This vector contains a Herpes simplex 
type I thymidine kinase (HS-tk) gene cDNA that is transcribed 
from the viral LTR and a bacterial neomycin resistance (NeoR) 
gene transcribed from an internal SV40 (simian virus 40) early 
promoter (LTR — HS-tk-SV-NeoR-LTR) in the G1 vector backbone 
(Genetic Therapy Inc., Gaithersburg, Md) . This Gl-based 
vector has been modified for increased safety by alteration 
of the gag start codon to a stop codon, and by elimination of 
viral sequences needed in trans for the formation of the virus 
particle. This has been shown to minimize the potential for 
the development of replication-competent virus production from 
producer cells which contain the vector. The HS-tk gene is 
a negative selectable marker or "suicide" gene. When a HS- 
tk transduced cell is exposed to GCV, the GCV acts as a 
substrate for phosphorylation by HS-tk resulting in a 
monophosphate (MP) form of the drug. Cellular phosphorylases 
converts this GCV-MP to GCV-triphosphate (GCV-TP) that 
inhibits DNA polymerase and is incorporated into DNA resulting 
in an | inability of the cell to proliferate. The end result 
is cell death for the HS-tk transduced cells (19, 23). The 
NeoR gene is a positive selectable marker. The bacterial 
NeoR gene encodes for NPT II (neomycin phosphortransf erase 
II), an enzyme that will protect GlTkSvNa.29 expressing cells 
from the toxic effects of G418 (a neomycin analog) . NeoR has 
been used in human clinical trials to date without adverse 
effect. 
Severe edema: Edema secondary to necrosis and destruction of 
the transduced tumor cells may occur. The magnitude of such 
edema, if it occurs at all, is unknown. As a precaution, all 
patients will be treated with high-dose steroids. If edema 
around the tumor is not responsive to therapy, permanent, 
significant neurological deficits or death may result. 
Surgical Procedures: The surgical procedures carry a risk for 
loss of neurological function, non-neurological complications 
and death. This risk depends on the preoperative condition 
of the patient, size and location of the tumor, and associated 
disease (e.g. renal failure, etc.). The individual risk will 
be determined prior to the decision on the line of therapy and 
will be discussed with the patient prior to surgery. 
Use of the Ommaya Reservoir. The Ommaya reservoir is a 
commonly us^d device in neurosurgery. The potential 
complications resulting from its use are infection and 
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