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The Antiviral Agent Cidofovir [(S)-1-(3-Hydroxy-2-phosphonyl-methoxypropyl) Cytosine] Has Pronounced Activity against Nasopharyngeal Carcinoma Grown in Nude Mice¹

Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina 27599-7295 [J. N., R. S., N. R-T., J. S. P.], and The Rega Institute for Medical Research, Katholieke Universiteit Leuven, 3000 Leuven, Belgium [J. N., E. D. C.]

The effect of the antiviral agent (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl) cytosine (cidofovir) on the EBV-associated tumor nasopharyngeal carcinoma (NPC) was evaluated in NPC xenografts in athymic mice. Intratumoral injection arrested tumor growth within 1 week, and by 4 weeks, tumors regressed to 8–75% (39 ± 33%) of the original size, whereas control tumors injected with PBS grew to 282 ± 25% of the original size. Ganciclovir slowed but did not arrest or cause regression of tumor growth. A striking antitumor effect was also produced by systemic administration; at 4 weeks, tumors were 79 ± 49% of the original size, compared with 635 ± 91% for the controls. Widespread apoptosis was detected after treatment for 2–6 days in C15 as well as two other NPC xenografts, C17 and C18; the latter NPCs have mutations in the p53 gene. These data indicate that cidofovir induces rapid cell death through apoptosis in EBV-transformed epithelial cells.

¹ Supported by National Cancer Institute Grants CA19014 (to J. S. P. and N. R-T.) and CA32979 (to N. R-T.). J. N. is a postdoctoral research Fellow from the Flemish Fonds voor Wetenschappe-lijk Onderzoek and is supported by the D. Collen Research Foundation/Belgian-American Educational Foundation.

² R. S. and J. N. contributed equally to this work.

³ To whom requests for reprints should be addressed, at the Lineberger Comprehensive Cancer Center, University of North Carolina, Campus Box 7295, Chapel Hill, NC 27599-7295.

Received 10/ 2/97. Accepted 12/29/97.

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