Thirty-one patients were treated at 6 dose levels ranging from 0.01 to 0.09 mg/kg and 7 had paired pre- and posttreatment biopsies (Poster AACR (Free AACR Whitepaper) 2011, Genprex, APR 2, 2011, View Source [SID:1234500633]). RT-PCR analysis detected high TUSC2 plasmid expression in 6 of 7 posttreatment tumor specimens but not in pretreatment specimens and negative controls. Immunohistochemical staining has been performed on one paired specimen, demonstrating low background TUSC2 protein staining in the pretreatment tissue compared with high intense TUSC2 protein staining in the posttreatment tissue. RT-PCR gene expression profiling analysis of apoptotic pathway genes in one paired specimen demonstrated significant upregulation and downregulation of genes involved in both the intrinsic and extrinsic apoptotic pathways. Among 4 patients treated without premedications, all 4 developed grade 2 or 3 fever. Among the 27 patients premedicated with dexamethasone and diphenhydramine, the highest fever was grade 2, which occurred in 2 subjects. The only dose-limiting toxicities were 2 episodes of transient grade 3 hypophosphatemia, resulting in an MTD of 0.06 mg/kg. Twentythree patients who received two or more doses were evaluable for response, with 5 achieving stable disease (2.6-10.8 months) and 18 progressing. One patient with stable disease had evidence of a durable metabolic response on positron emission tomography imaging. The pretreatment apoptotic index was predictive of disease stability. Median survival time was 9.1 months.

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