48 hours after the last injection. 
6.0 pre-trea™emt evaluation 
6.1 A complete history and physical to include performance status, recent weight loss, usual weight 
and concurrent non-mal ignant disease and its therapy, and all prior anticancer treatments must be 
recorded. 
6.2 Laboratory studies shall include quantitative immunoglobulins; a CBX with differential and 
platelet count; SMA-12 and electrolytes, including creatinine, bilirubin, SGPT, alkaline 
phosphatase, urinalysis, and chest x-ray. 
6.3 Any residual toxicity from prior therapies should be recorded using the grading schema in 
Appendix C. 
6.4 Appropriate studies should be obtained to fully define the extent and severity of existing or 
suspected malignant and non-mal ignant disease. 
6.5 The location and size of the endobronchial lesion must be recorded prior to treatment. A 
photograph of the area will be taken at a fixed distance from the lesion. The area will be 
measured in 2 dimensions (product of longest and perpendicular dimensions). 
7.0 EVALUATION DURING STUDY 
7.1 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 retroviral proteins. 
7.2 History and physical with performance status and weight should be recorded before each course. 
7.3 The tumor will be photographed bronchoscopical ly at the beginning of each course. Tumor 
measurements are to be recorded before each course. 
7.4 All relevant information regarding drug dosage, tumor response, laboratory examinations, and 
treatment-related toxicities must be recorded before each treatment is given. 
7.5 Parameters to be Measured In Vitro 
7.5.1 Bronchoscopic tumor and normal bronchial epithelial biopsies will be obtained prior to 
the beginning of each course. Tissue will be fixed immediately in 4X paraformaldehyde and 
0.5X gluteraldehyde at 4"C. This will permit extraction of DNA and RNA and permit in situ 
hybridization. 
7.5.2 Biopsies will be analyzed for incorporation of the transduced gene into the host genomic 
DNA and expression of the transduced gene at the RNA level by standard hybridization 
techniques following polymerase chain reaction and by in situ hybridization. 
7.5.3 All patients will be evaluable for response and toxicity following one course of therapy 
7.6 An autopsy will be requested on all patients enrolled in the protocol who die. DNA will be 
extracted from tumor and normal tissues to determine if the retroviral vector is integrated. PCR 
amplification of specific sequences will be used to determine this. 
7.7 Three blood samples will be collected at one-half hour intervals following injection of the 
retroviral supernate. These samples will provide leukocytes to analyze for integration of 
retroviral DNA. Serum will be tested for antibodies to retroviral envelope proteins. This will 
be done by western blot analysis performed by Microbiological Associates, Inc. (Rockville, MD). 
Patients will be tested monthly during treatment, monthly for the first three months following 
completion of treatment, every three months for the remainder of the year following completion of 
treatment, and then at least yearly thereafter. 
7.8 Normal tissue samples will be collected during the follow-up visits and bronchoscopies. These 
will include samples of normal bronchial mucosa, leukocytes, and germ cells. These tissues will 
be analyzed for incorporation of the retrovirus. 
8.0 CRITERIA FDR RESPDNSE AND TOXICITY 
8.1 The tumor bed will be photographed prior to each course of therapy. 
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