PROTOCOL THS 94-002 
REVISED 5/19/94 
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Pr etreatment and Treatment Evaluation: 
Patients will have a CBC, platelet count, PT, PTT, SMA-12, electrolytes, and a chest x-ray 
i prior to each course of therapy. Serum will be collected pre- and post-treatment for analysis 
' of antibodies to adenovirus proteins. 
I The endobronchial tumors will be photographed bronchoscopically at the beginning of each 
I course. Tumor measurements are to be recorded before each course for ail measurable tumors. 
Fine needle aspirates or core biopsies will be obtained of accessible local tumor. Cells in the 
' cytospins of pleural effusions will be obtained pre- and post-treatment when possible. For 
I endobronchial tumors bronchoscopic tumor and normal bronchial epithelial biopsies will be 
■ obtained prior to the beginning of each course. Tissue will be fixed immediately in 4% 
paraformaldehyde and 0.5% gluteraldehyde at 4°C. This will permit extraction of DNA and 
■ RNA and permit in situ hybridization. 
j Biopsies will be analyzed for incorporation of the transduced gene into the host genomic DNA 
I and expression of the transduced gene at the RNA level by standard hybridization techniques 
j following polymerase chain reaction and by in situ hybridization. 
I All patients will be evaluable for response and toxicity following one course of therapy. 
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scellaneous Information: 
Not applicable 
St atistical Considerations: 
Three patients will be entered at each dose level with 6 patients entered 
at the maximum tolerated or maximum attainable dose (limitations imposed 
by production of the adenovirus) . A maximum of 21 patients will be 
entered in the intratumor and the intrapleural groups, respectively for 
each of the treatment groups (Ad5CMV-p53 alone and Ad5CMV-p53 plus 
cisplatin) . 
Ob jectives : . 
1 . To determine the maximum tolerated dose of the wild-type p53 adenovirus vector 
given with and without cisplatin in patients with refractory non-small cell lung 
cancer. 
2. To determine the qualitative and quantitative toxicity and reversibility of toxicity 
of this treatment approach. 
3. To document observed antitumor activity of this treatment approach. 
Recombinant DNA Research, Volume 19 
[589] 
