Combined radiation and enzyme/prodrug treatment for head and neck cancer in an orthotopic animal model

In an effort to improve the therapeutic outcome for squamous cell cancer of the head and neck, we have used the enzyme cytosine deaminase (CD) and the prodrug 5-fluorocytosine (5-FC) as a means to deliver the chemotherapeutic agent 5-fluorouracil (5-FU) in a tumor-specific manner and have evaluated the use of this treatment in combination with external-beam radiation, Infe ction of SCCVII cells in culture with a CD-expressing retrovirus and treatm ent with 5-FC was cytotoxic depending on the time of treatment and dose of 5-FC, An orthotopic model of squamous cell cancer of the head and neck was used in vivo to study the CD/5-FC system both alone and with concurrent rad iation due to the radiosensitizing properties that 5-FU generates in situ, Treated mice were imaged using magnetic resonance imaging (MRI), and their survival was evaluated. Neither 5-FU nor radiation either alone or combined provided a survival advantage, In contrast, 5-FC treatment prolonged survi val and decreased tumor burden compared to control animals, but the tumors recurred after the treatment ceased. Finally, combined treatment with concu rrent administration of 5-FC and radiation resulted in a synergistic decrea se in tumor growth and enhanced survival over treatment with 5-FC or radiat ion alone. (C) 1999 by Radiation Research Society.