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Phase I and biodistribution study of recombinant adenovirus vector-mediated herpes simplex virus thymidine kinase gene and ganciclovir administration in patients with head and neck cancer and other malignant tumors

Cancer Gene Therapy volume 16, pages 723–730 (2009)Cite this article

Abstract

In this study, we investigated the safety and efficacy in cancer patients of a single intra-tumor injection of recombinant adenovirus vector-mediated herpes simplex virus thymidine kinase gene (AdV/TK) followed by systemic administration of ganciclovir (GCV). In 18 patients with malignant tumors refractory to standard treatment, AdV/TK was injected on day 1 with dose escalation from 2.5 × 1011 to 1 × 1012 virus particles (VP), and GCV (5 mg kg−1) was delivered intravenously every 12 h from days 2 to 15. The most common treatment-related toxicities were transient fever (10/18) and local injection site reaction (10/18), and most adverse events were WHO grade I/II. Anti-adenovirus antibody levels increased continuously during treatment, but anti-HSV antibody levels remained stable. One patient had a PR at the injection site but PD was found in the primary site (lung cancer), one patient with fibrosarcoma of the neck had an MR, five patients had SD, and 10 patients had PD. In conclusion, AdV/TK followed by GCV can be administered safely to Chinese cancer patients, and achieved a local response with few environmental effects. Because the response was localized, single regional tumor relapse, especially after radiation, may be an indication for this suicide gene therapy.

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Authors and Affiliations

  1. State Key Laboratory of Oncology in Southern China, Sun Yat-sen University, Guangzhou, Guangdong, PR China

    F Xu, S Li, X-L Li, Y Guo, B-Y Zou, R Xu, H Liao, H-Y Zhao, Y Zhang, Z-Z Guan & L Zhang

  2. Department of Medical Oncology, Cancer Center, Sun Yat-sen University, Guangzhou, Guangdong, PR China

    F Xu, S Li, X-L Li, Y Guo, B-Y Zou, R Xu, H Liao, H-Y Zhao, Y Zhang, Z-Z Guan & L Zhang

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  1. F Xu
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Correspondence to L Zhang.

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Xu, F., Li, S., Li, XL. et al. Phase I and biodistribution study of recombinant adenovirus vector-mediated herpes simplex virus thymidine kinase gene and ganciclovir administration in patients with head and neck cancer and other malignant tumors. Cancer Gene Ther 16, 723–730 (2009). https://doi.org/10.1038/cgt.2009.19

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  • DOI: https://doi.org/10.1038/cgt.2009.19

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