and intentionally exposed to large amounts of infectious replication-competent 
retrovirus), n£ untoward effects of retroviral exposure or retroviral-mediated gene 
transfer have been observed (20) (Appendix E). Based upon available data, the risk of 
death secondary to their tumor far exceeds any risk of insertional mutagenesis. 
G. Ganciclovir sodium (GCV: Cytovene®) 
The GCV used in this trial will be purchased from Syntex corporation (Palo 
Alto, CA). GCV is an FDA approved drug for the treatment of cytomegalovirus (CMV) 
retinitis in immunocompromised individuals. The drug is administered by intravenous 
infusion over 1 hour at a dose of 5 mg/kg of body weight twice daily for 1 4-21 days. 
FDA approved prescribing guidelines (where applicable), administration procedures, 
drug interactions, and patient monitoring recommendations will be followed for the use 
of this drug. The Cytovene® product monograph is included in appendix F. 
There is no information regarding the use of GCV for the treatment of 
humans as a method to destroy herpes TK gene transduced human cells. GCV does 
cross the blood-brain barrier. The cerebral spinal fluid (CSF)/plasma ratios has been 
estimated in 3 patients at various time intervals with ratios ranging from 0.24 to 0.7 
(0.31-0.68 jag/ml in the CSF and 0.44-2.20 pg/ml in the plasma). Peak plasma levels 
have been documented to reach 9|ig/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 (0.5p.g/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. 
The most common side effects are granulocytopenia (absolute neutrophil 
count (ANC) of <1000 cells/mm 3 ) in 40% of patients and thrombocytopenia (< 50,000 
platelets/mm 3 ) in 20%. This data was collected in immunosuppressed, CMV infected 
AIDS patients, who may have been more susceptible to marrow suppression than our 
patient population, due to additional opportunistic infections and concomitant drug 
therapy. The actual risk to our patient population 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 until the ANC is >750 cells/mm 3 platelet 
Recombinant DNA Research, Volume 15 
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