sole reason for the biopsy. K-ras mutations will be determined by specific 
oligonucleotide hybridization to PCR amplified tumor DNA. Mutations of the p53 
gene will be determined by SSCP analysis of exons 5-8 of PCR amplified tumor 
DNA. 
4.6 Patients will be tested for HIV prior to entry onto the protocol and must be HIV- 
negative. 
5.0 TREATMENT PLAN 
5.1 Patients will undergo bronchoscopy to assess the degree of obstruction. As 
much gross tumor as possible will be resected endoscopically. Patients may 
also have had brachytherapy as a tumor reduction modality. 
5.2 Patients will undergo bronchoscopy under topical or general anesthesia. A 
Stifcor tm transbronchial aspiration needle (21 g) will be passed through the 
biopsy channel of the bronchoscope. The residual tumor site will be injected 
with 10 7 CFU of the appropriate retroviral supernate. The volume will be no 
greater than 10 ml. Protamine will be added at a concentration of 5pg/ml. This 
is 0.2% of the amount given intravenously to reverse heparinization. 
Injections will be circumferential and will be intratumor and submucosal. The 
AS-K -ras supernate will be used for K-ras mutations and the p53 supernate will 
be used for p53 mutations. The injections will be repeated daily for five 
consecutive days. The treatment will be repeated monthly. Treatment will 
continue as long as there is no tumor progression. After one year the patients 
will be evaluated for continuation of therapy. 
5.3 Patients will wear a surgical mask for 24 hours following injection of the 
retroviral supernate. All medical personnel will wear masks routinely during 
bronchoscopy and injection of the retroviral supernates. Anti-tussives will be 
prescribed as necessary. 
6.0 PRE-TREATMENT EVALUATION 
6.1 A complete history and physical to include performance tatus, recent weight 
loss, usual weight and concurrent non-malignant 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, and 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 
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