PROTOCOL THS 94-002 
REVISED 5 / 19/94 
PAGE 13 
to drug administration. All required interim and pretreatment data should be available and the 
physician must have a designation as to tumor response and toxicity grade. 
10.2 Data Entr y: Data must be entered into the Clinical Data Management System before a course of 
therapy can be given. A brief explanation for missing data should be recorded as a comment. 
10.3 Accuracy of Data Collection: The Study Chairperson will be the final arbiter of response of toxicity 
should a difference of opinion exist. 
1 1 .0 STATISTICAL EVALUATION 
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). | 
12.0 REFERENCES 
1. Brown CC, Kessler LG. Projections of lung cancer mortality in the United States: 1985-2025. J Natl Cancer 1 
Inst 1988:80:43. 
2. Bishop JM. Molecular themes in oncogenesis. Cell 1991;64:235-248. 
3. Hollstein M, Sidransky D, Vogelstein B, Harris CC. p53 mutations in human cancers. Science 
1991;253:49-53. 
4. Lane DP, Benchimd S. p53: oncogene or anti-oncogene? Genes & Develop 1990;4:1-8. 
5. Bressac B, Galvin KM, Liang TJ, Isselbacher KJ, Wands JR. Abnormal structure and expression of p53 gene 
in human heptatocellular carcinoma. Proc Natl Acad Sci USA 1990;87:1973-1977. 
6. Dolcetti R, Maestro R, Feriotto G, Pelucchl S, Rizzo S, Boiocchi M. p53 genetic abnormalities in human 
squamous cell carcinomas of the larynx Oncogene 1990;6:44-45. 
7. Rodrigues NR, Rowan A, Smith MEF, et al. p53 mutations in colorectal cancer. Proc Natl Acad Sci USA 
1990;87:7555-7559. 
8. Nigro JM, Baker SJ, Preisinger AC, et al. Mutations in the p53 gene occur in diverse human tumor types. 
Nature 1989;342:705-708. 
9. Takahashl T, Nau MM, Chiba I, et al. p53: a frequent target for genetic abnormalities in lung cancer. Science 
1989;246:491-494. 
10. Mukhopadhyay T, Cavender A, Tainsky M, Roth JA. Expression of antisense K-ras message in a human lung 
cancer cell line with a spontaneous activated K-ras oncogene alters the transformed phenotype. Proc Amer 
Assoc Cancer Res 1990;31:304. 
11. Meltzer SJ, Yin J, Huang Y, et al. Reduction to homozygosity involving p53 in esophageal cancers 
demonstrated by the polymerase chain reaction. Proc Natl Acad Sci USA 1991;88:4976-4980. 
12. Soriano P, Montgomery C, Geske R, Bradley A. Targeted disruption of the c-src proto-oncogene leads to • 
osteopetrosis in mice. Cell 1991;64:693-702. 
13. Chen P-L, Chen Y, Bookstein R, Lee W-H. Genetic mechanisms of tumor suppression by the human p53 
gene. Science 1990;250:1576-1580. 
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