Tiazofurin: A new antitumor agent

Peter J. O'Dwyer, D. Dale Shoemaker, Hiremagalur N. Jayaram, David G. Johns, David A. Cooney, Silvia Marsoni, Louis Malspeis, Jacqueline Plowman, J. Paul Davignon, Ruth D. Davis

Research output: Contribution to journalArticle

33 Scopus citations

Abstract

Tiazofurin is an interesting drug now entering Phase I trials, with marked preclinical antitumor activity against P388 and L1210 leukemias, and the Lewis lung carcinoma. Schedule dependency favoring frequent administration has been noted. The drug has a novel mechanism of action, being metabolized to an inhibitory cofactor of inosine monophosphate dehydrogenase. Tiazofurin is widely distributed after i.v. administration exhibiting a triphasic pattern of plasma decay, with a terminal half-life of 3-16 h in the three species studied. Approximately 90% of the drug was excreted unchanged in the urine within 24 h. A significant potential for the slower release of intracellularly retained drug exists. Anticipated organ toxicities based on the studies described include myelotoxicity, hepatotoxicity and nephrotoxicity. These were mild and reversible at lower doses, and were not seen at levels corresponding to the starting doses in man. A potential for hyperuricemia exists; this should be easily controllable by the use of allopurinol, without compromising the drug's antitumor effect. Phase I trials under the sponsorship of the NCI are underway in a number of institutions.

Original languageEnglish (US)
Pages (from-to)79-84
Number of pages6
JournalInvestigational New Drugs
Volume2
Issue number1
DOIs
StatePublished - Mar 1 1984

    Fingerprint

Keywords

  • tiazofurin

ASJC Scopus subject areas

  • Oncology
  • Pharmacology
  • Pharmacology (medical)

Cite this

O'Dwyer, P. J., Shoemaker, D. D., Jayaram, H. N., Johns, D. G., Cooney, D. A., Marsoni, S., Malspeis, L., Plowman, J., Davignon, J. P., & Davis, R. D. (1984). Tiazofurin: A new antitumor agent. Investigational New Drugs, 2(1), 79-84. https://doi.org/10.1007/BF00173791