The antiviral agent cidofovir [(S)-1-(3-hydroxy-2-phosphonyl-methoxypropyl)cytosine] has pronounced activity against nasopharyngeal carcinoma grown in nude mice

Cancer Res. 1998 Feb 1;58(3):384-8.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Animals
  • Antiviral Agents / therapeutic use*
  • Apoptosis / drug effects
  • Carcinoma / drug therapy*
  • Carcinoma / genetics
  • Carcinoma / pathology
  • Carcinoma / virology
  • Cidofovir
  • Cytosine / analogs & derivatives*
  • Cytosine / therapeutic use
  • Drug Screening Assays, Antitumor
  • Female
  • Ganciclovir / pharmacology
  • Ganciclovir / therapeutic use
  • Genes, p53
  • Herpesviridae Infections / drug therapy*
  • Herpesviridae Infections / pathology
  • Herpesviridae Infections / virology
  • Herpesvirus 4, Human / drug effects*
  • Herpesvirus 4, Human / pathogenicity
  • Humans
  • Injections, Intralesional
  • Mice
  • Mice, Nude
  • Nasopharyngeal Neoplasms / drug therapy*
  • Nasopharyngeal Neoplasms / genetics
  • Nasopharyngeal Neoplasms / pathology
  • Nasopharyngeal Neoplasms / virology
  • Neoplasm Transplantation
  • Organophosphonates*
  • Organophosphorus Compounds / therapeutic use*
  • Tumor Virus Infections / drug therapy*
  • Tumor Virus Infections / pathology
  • Tumor Virus Infections / virology

Substances

  • Antiviral Agents
  • Organophosphonates
  • Organophosphorus Compounds
  • Cytosine
  • Cidofovir
  • Ganciclovir