Scientific Abstract 
Patient Eligibility: Patients must have histologic proof of non-small cell lung cancer. Patients must be 
either unresectable, unable to receive primary external beam radiation therapy, or have failed primary 
external beam radiation therapy, or have failed chemotherapy. 
Patients must have either an endobronchial tumor accessible by the bronchoscope, with some clinical 
evidence of bronchial obstruction, advanced local-regional cancer which is unresectable, or malignant 
pleural effusion. 
All patients must have a life expectancy of at least 1 2 weeks and must have a performance status of 
j<2 (Zubrod scale. Appendix B). 
A tumor biopsy must show a p53 mutation by single-strand conformation analysis. 
Patients will be tested for HIV prior to entry onto the protocol and must be HIV-negative. 
Patients must have adequate bone marrow function (defined as peripheral absolute granulocyte count 
of >2,000/mm^ and platelet count of 1 00,000/mm^), adequate liver function (bilirubin ^1.5 mg/dl), and 
adequate renal function (creatinine <1.5 mg/dl). 
Treatment Plan : The study will be done in two phases for each patient. It is not known what toxicities if 
any will be caused by the adenovirus. The first phase of the study will allow assessment of toxicities 
related only to the vector. Patients will receive one intratumor or intrapleural injection of Ad5CMV-p53. 
The initial dose will be 10® plaque forming units (PFU). Following completion of the first vector-alone 
injection, a second phase will evaluate Ad5CMV-p53 and cisplatin administered concurrently. Two 
weeks later the patient will receive one intratumor or intrapleural injection of Ad5CMV-p53 at the same 
dose as the first injection with concurrent cisplatin at 30 mg/m^ with 2 additional doses of cisplatin on 
days 2 and 3. Three patients will be entered at each dose level with 6 patients entered at the maximum 
tolerated or maximum attainable dose (limitation imposed by production of the adenovirus). The 
adenovirus dose will increase in one logio increments for each group. Patients entered at a given dose 
level will not be eligible for dose escalation. Dose escalation will proceed separately for the intratumor 
injection group and the intrapleural injection group. The dose of cisplatin will remain constant. 
Patient Evaluation : Patients will have a CBC, platelet count, PT, PTT, SMA-12, electrolytes, and a chest 
x-ray prior to each course of therapy. Serum will be collected pre- and post-treatment for analysis of 
antibodies to adenovirus proteins. 
The endobronchial tumors will be photographed bronchoscopically at the beginning of each course. 
Tumor measurements are to be recorded before each course for all 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 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. 
Biopsies will be analyzed for uptake of the transduced gene by DNA PCR and expression of the 
transduced gene at the RNA level by standard hybridization techniques following polymerase chain 
reaction and by in situ hybridization. 
All patients will be evaluable for response and toxicity following one course of therapy. 
Statistical 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 each phase of the study. 
Objectives : 
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 
[583] 
