Abstract
The aim of this phase I clinical trial was to assess the feasibility and safety of intratumoral administration of a first-generation adenoviral vector encoding herpes simplex virus thymidine kinase (HSV-TK) gene (Ad.TK) followed by systemic ganciclovir to patients with advanced hepatocellular carcinoma (HCC). Secondarily, we have analyzed its antitumor effect. Ten patients were enrolled in five dose-level cohorts that received from 1010 to 2 × 1012 viral particles (vp). Ad.TK was injected intratumorally and patients received up to three doses at 30-day intervals. Positron emission tomography was used to monitor TK gene expression. Ad.TK injection was feasible in 100% of cases. Treatment was well tolerated and dose-limiting toxicity was not achieved. Cumulative toxicity was not observed. Hepatic toxicity was absent even in cirrhotic patients. Fever, flu-like syndrome, pain at the injection site and pancytopenia were the most common side effects. No partial responses were observed and 60% of patients showed tumor stabilization of the injected lesion. Importantly, two patients who received the highest dose showed signs of intratumoral necrosis by imaging procedures. One of them achieved a sustained stabilization and survived for 26 months. In conclusion, Ad.TK can be safely administered by intratumoral injection to patients with HCC up to 2 × 1012 vp per patient.
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Acknowledgements
CIBERehd is funded by the Instituto de Salud Carlos III. This work has been funded in part by Fundación Areces and Accion Transversal contra el Cancer. We thank Maria Eugenia Cornet, Maria del Mar Municio, Viñas Andrés and Elena del Corral for their work in trial monitoring.
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Sangro, B., Mazzolini, G., Ruiz, M. et al. A phase I clinical trial of thymidine kinase-based gene therapy in advanced hepatocellular carcinoma. Cancer Gene Ther 17, 837–843 (2010). https://doi.org/10.1038/cgt.2010.40
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DOI: https://doi.org/10.1038/cgt.2010.40
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