Metastatic or non-resectable (stage IV) pancreatic cancer has a rapidly fatal outcome (median survival: 3-6 months), thus making gene therapy a viable therapeutic option. The objectives of the clinical studies are to evaluate the safety/toxicity and potential anti-tumor response/efficacy of intravenous (i.v.) infusions of a ‘pathotropic’ retroviral vector bearing a cytocidal gene construct (Rexin-G) as a gene transfer intervention for stage IV pancreatic cancer. An intra-patient dose escalation regimen was used wherein increasing doses of Rexin-G were given i.v. daily for 8-10 days. Completion of this regimen was followed by a one-week evaluation period for toxicity, after which, the maximum tolerated dose of Rexin-G was administered for another 8-10 days. In a second protocol, i.v. Rexin-G was administered frontline for 6 days followed by 8 doses of weekly gemcitabine. The NIH Common Toxicity Criteria Vs.2 was used to assess toxicity, and the NCI-RECIST criteria and tumor volume measurements were used to evaluate potential anti-tumor responses. We report the results of the first 3 patients that participated in the studies. Rexin-G arrested tumor growth in 3 of 3 patients without experiencing dose-limiting toxicity. No bone marrow suppression, significant alterations in liver and kidney function, nausea and vomiting, mucositis or hair loss were observed. Two patients are alive with stable disease ≈5 and 14 months from diagnosis, and 1 patient is alive with progressive disease 20 months from diagnosis. The encouraging results of this first clinical experience will guide the design and planning of phase I/II clinical trials to establish the safety and efficacy of Rexin-G as the first targeted injectable gene therapy vector for stage IV pancreatic cancer.

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