p53 transduction efficiency and stability: 
Proportion of tumor and normal cells expressing transduced wild-type p53. 
Level of wild-type p53 expression in transduced cells. 
Phenotypic effects: 
Cytologic changes associated with ACN53 infection and/or wild-type p53 
transduction, as determined by histopathologic examination of normal and 
malignant ussue. 
Inflammatory response: 
Evidence of inflammation as determined by histopathologic examination of 
normal and malignant tissue. 
7.10.3 Methodology: See Appendix G. 
8.0 POTENTIAL TOXICITY, DOSE MODIFICATIONS, AND MANAGEMENT 
8. 1 Toxicity will be assessed using the University of California, San Francisco (UCSF) 
Toxicity Criteria (Appendix C). Toxicity will be formally evaluated on Days 1-3, 7, 
14, 21, 28, then every 2 months for one year, then yearly (see Section 7.0). 
8.2 Definitions 
8.2.1 A dose-limiting toxicity (DLT) will be defined in this study as any grade 4 toxicity 
or any grade 3 toxicity persisting more than 1 week. Nausea, vomiting, anorexia, 
and alopecia will be excluded as dose-limiting toxicities. 
8.2.2 The maximum tolerated dose (MTD) will be defmed in this study as that dose level 
immediately below the level associated with dose-limiting toxicity in at least 3 out of 
6 patients treated at that dose level. 
8.3 Dose Modifications 
8.3.1 If one of the three patients treated with ACN53 at a given dose level experience 
a dose-limiting toxicity (DLT), up to three additional patients will be entered at that 
dose level (see Section 6.3.4, Dose Escalation) 
8.3.2 If three of the initial patients treated with ACN53 at Dose Level 1 experience a DLT, 
the next three patients will be entered at Dose Level 0. 
8.3.3 If Dose Level 0 exceeds the maximum tolerated dose, the study will be 
terminated. 
8.3.4 No patient will receive treatment at a dose level greater than the DLT. 
8 . 4 Criteria for Post-T reatment Laparotomy 
Patients who have elected to undergo exploratory laparotomy with potential placement of a 
hepatic artery infusion pump following ACN53 therapy will proceed to laparotomy if and 
only if all of the following are true at the time of the Day 7 Evaluation or later: 
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