brain or a mild, self-limited infection if formed outside the brain. The protocol 
calls for microbiological tests to detect the shedding of both recombinant and 
wild type virus. 
C. Potential Biohazard Exposure to Healthcare Personnel: 
1. Surgical personnel: There is a low potential for biohazard exposure to the surgical 
personnel. The viral vector is suspended in a small volume (<1 .0 ml) of buffer 
and is contained in a septum vial. The syringe is loaded from the vial with no 
virus vector loss. Intratumoral injection is made and the amount of leakage 
along the needle track is likely to be very minute. In the event of accidental spills 
of the virus from the vial common disinfectants can be used to inactivate the 
agent. All surgical personnel are instructed on the safe use and potential 
biological hazards of the virus vector before the procedures are performed. 
2. Post-surgical healthcare workers: There is a potential that ADV/RSV-tk virus may 
escape the patient via urine, feces, saliva, mucus, tears or other excretions. 
Studies in non-human primates indicate that the potential is low since studies 
show that only one plaque was detected in the serum of one baboon of 6 that 
were injected 2 days previously with the vector. (Appendix B). Exposure to 
shedded replication-defective virus will pose a very limited hazard as the titers 
will be extremely low. There is a theoretical possibility that the vector could 
recombine with wild type adenovirus harbored by the patient (see above). 
Infection with this virus would cause a mild, self-limited infection similar to a 
common adenovirus infection. Until it has been proven by microbiological tests 
that the patient is not shedding virus strict biohazard procedures will be 
practiced. Healthcare workers will be instructed on the safe use and potential 
biological hazards of the virus vector before they are allowed to work with the 
patients. 
D. Ganciclovir Sodium (GC V; Cytovene®). 
Ganciclovir (Cytovene®), used in this trial is manufactured by Syntex Corporation 
(Palo Alto, CA). The drug is approved for the treatment of CMV retinitis in the 
immunocompromised patient and for the prevention of CMV disease in transplant patients at 
risk for CMV disease. The intravenous form will be used in this protocol. It will be 
administered IV over one hour at 5 mg/kg/dose twice daily (q 12 hours) for 14 days 
beginning 24 hours after virus injection (total doses = 28 ). 
For IV administration, ganciclovir is supplied in 10 ml vials containing lyophilized 
ganciclovir sodium powder equivalent to 500 mg ganciclovir and 46 mg sodium. The 
lyophilized powder is stable for 42 months at 25° C (77° F). The reconstituted solution is 
stable for at least 12 hours at 25° C in Sterile Water for Injection. Admixture preparations in 
0.9% Sodium Chloride are stable for at least 24 hours when refrigerated. 
Clinical studies of intravenous ganciclovir have been performed at the 10 mg/kg/day 
dose that will be used in this protocol. The drug is excreted in the urine largely 
unmetabolized (90%). Plasma protein binding is only 1-2%. Plasma levels at the end of a 
one hour infusion were an average of 8.3 mg/ml (±_4.0). Trough levels 1 1 hours after 
infusion were 0.56 mg/ml (± 0.66). The plasma half-life was 2.9 hours (± 1.3). 
Recombinant DNA Research, Volume 20 
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