H. 
I. 
of injection of the producer cells. Based upon available 
data, the risk of death secondary to their tumor far exceeds 
any risk of insertional mutagenesis. 
Ganciclovir sodium (GCV; Cytovene ) . The GCV used in this 
trial will be obtained from Syntex Corporation (Palo Alto, 
CA) . GCV is an FDA approved drug for cytomegalovirus (CMV) 
retinitis therapy in immunocompromised individuals. The drug 
is given by IV infusion over 1 hour (dose of 5 mg/kg) twice 
daily for 14-21 days. FDA approved guidelines (where 
applicable) , administration procedures, drug interactions, and 
patient monitoring will be followed. There is minimal 
information regarding the use of GCV for the treatment of 
humans as a method to destroy HS-tk gene transduced human 
cells. Further information about toxicity is being generated 
in the initial NIH trial. To date, no toxicities have been 
noted in the first four patients. 
GCV has been noted to cross the blood-brain barrier. The 
cerebral spinal fluid (CSF) plasma ratio has been estimated 
in 3 patients at various time intervals with ratios ranging 
from 0.24 to 0.7 (0.31-0.68 ug/mL in the CSF and 0.44-2.20 
ug/mL in the plasma) . Peak plasma levels have been documented 
to reach 9ug/mL. These CSF and plasma levels are expected to 
be within the range of GCV levels needed to kill the HS-tk 
transduced cells based on in vitro studies (0.5 ug/mL will 
prevent growth of HS-tk transduced tumor cells) . If the 
patient has evidence of renal impairment, the dose will be 
adjusted as suggested in the GCV monograph. 
Granulocytopenia (absolute neutrophil count (ANC) of <1000 
cells/mm 3 ) in 40% of patients and thrombocytopenia (<50,000 
platelets/mm 3 ) in 20% are the most frequent side effects. This 
data was collected in CMV infected AIDS patients, who may have 
been more susceptible to marrow suppression, due to other 
opportunistic infections or drug therapy. The actual risk to 
our patients is unknown. Each patient will be closely 
monitored for the development of granulocytopenia and 
thrombocytopenia. The development of an ANC of <500 cells/mm 3 
or a platelet count of <25,000 platelets/mm 3 will require a 
dose interruption or decrease until the ANC is >750 cells/mm 3 
platelet count is >40,000 platelets/mm 3 . Other side effects 
occurring in approximately 2% of patients include anemia, 
fever, rash and abnormal liver function. Fever and chills 
will be treated with acetaminophen (650 mg every 4 hours) and 
rash with diphenhydramine (50 mg every 6 hours) . See the 
monograph for complete toxicity criteria. Our treatment 
protocol will use the known tolerated dose ( lOmg/kg/day ) in 
non-inf ected patients for only 14 days. 
Statistics. Historical data on the survival of patients 
following re-operation for recurrent primary brain tumors will 
serve as a historical control. This is a two arm study with 
patient's divided into groups based on the resectibility of 
their tumor. Because treatment is not randomized and the 
treatment arms are similar, we will consider this a 
prospective, single arm trial to determine the response rate 
of this therapy for statistical purposes. A therapy with a 
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