Protocol HNS 94-001 
October 4, 1994 
Page 13 
10.0 
11.0 
12.0 
1 . 
2 . 
3. 
4. 
5. 
6. 
7. 
8 . 
9. 
10 . 
11 . 
9.5 Criteria for removal from protocol: 
a) Refusal to continue study participation 
b) Significant hemoptysis 
c) Coagulopathy 
d) Progressive pneumonitis or other infectious processes. 
DATA AND PROTOCOL MANAGEMENT 
10.1 Protocol Compliance: The attending physician and oncology research nurse must see patients prior 
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 Entry: 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. 
i- 
10.3 Accuracy of Data Collection: The Study Chairperson will be the final arbiter of response of toxicity 
should a difference of opinion exist. 
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 into each study group, for a total of 42 patients for the entire study. 
REFERENCES 
Van der Riet, P., Nawroz, H., Hruban, R.H., Corio, R., Tokino, K., Koch, W., and Sidransky, D. Frequent loss 
of chromosome 9 p21-22 early in head and neck cancer progression. Cancer Res 1994; 54: 1156-1158. 
Bishop JM. Molecular themes in oncogenesis. Cell 1991 ;64:235-248. 
Hollstein M, Sidransky D, Vogelstein B, Harris CC. p53 mutations in human cancers. Science 
1991;253:49-53. 
Lane DP, Benchimol S. p53: oncogene or anti-oncogene? Genes & Develop 1990;4:1-8. 
Bressac B, Galvin KM, Liang TJ, Isselbacher KJ, Wands JR. Abnormal structure and expression of p53 gene 
in human hepatocellular carcinoma. Proc Natl Acad Sci USA 1990;87:1973-1977. 
Dolcetti R, Maestro R, Feriotto G, Pelucchi S, Rizzo S, Boiocchi M. p53 genetic abnormalities in human 
squamous cell carcinomas of the larynx. Oncogene 1990;6:44-45. 
Rodrigues NR, Rowan A, Smith MEF, et al. p53 mutations in colorectal cancer. Proc Natl Acad Sci USA 
1990;87:7555-7559. 
Nigro JM, Baker SJ, Preisinger AC, et al. Mutations in the p53 gene occur in diverse human tumor types. 
Nature 1989;342:705-708. 
I 
Maestro, R., Dolcetti, R., Gasparotto, D., Doglioni, C., Pelucchi, S., Barzan, L., Grandi, E., and Boiocchi, M. 
High frequency of p53 gene alterations associated with protein overexpression in human squamous cell 
carcinoma of the larynx. Oncogene 1992; 7: 1159-1166. Jj 
Chung, K.Y., Mukhopadhyay, T., Kim, J., Casson, A., Ro, J.Y., Goepfert, H., Hong, W.K., Roth, J.A. 
Discordant p53 gene mutations in primary head and neck cancers and corresponding second primary cancers : 
of the upper aerodigestive tract. Cancer Res 1993; 53: 1676-1683. 
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 
$ l 
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