Tiazofurine ICN Pharmaceuticals

Curr Opin Investig Drugs. 2000 Oct;1(2):257-62.

Abstract

Tiazofurine is a nucleoside analog with oncolytic activity being developed by Ribapharm (formerly ICN Pharmaceuticals) as a potential treatment for leukemia. It is metabolized to TAD (thiazole-4-carboxamide adenine dinucleotide), an inhibitor of IMP dehydrogenase. This inhibition results in the reduction of guanylate levels and the halting of neoplastic proliferation. The compound is in phase II/III trials [215553]. It is expected that Ribapharm will file an orphan drug application for tiazofurine, as a treatment for myelogenous leukemia, following the drug's completion of phase III trials by the end of 2002. The company has reported that phase III trials will begin by the end of 2000. Preliminary studies involving 21 patients have been carried out and the results reported by the company. During these studies, seven patients with chronic myelogenous leukemia had a complete hematologic response and two patients had a partial response. Of the patients with a complete response, six had marrow and peripheral responses. Ribapharm, through a Russian subsidiary of ICN, is also planning to conduct phase II studies of tiazofurine involving patients suffering from advanced ovarian cancer or multiple myeloma which is resistant to conventional therapy. The company has reported that the multiple myeloma limited phase II study is still undergoing planning, with an intended start date in late 2000 [381453]. In March 2000, Chase Hambrecht & Quist predicted that first approval could be towards the end of 2001 [384894].

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Antineoplastic Agents / toxicity
  • Clinical Trials as Topic
  • Contraindications
  • Drugs, Investigational / adverse effects
  • Drugs, Investigational / chemical synthesis
  • Drugs, Investigational / metabolism
  • Drugs, Investigational / pharmacology*
  • Drugs, Investigational / therapeutic use
  • Drugs, Investigational / toxicity
  • Enzyme Inhibitors / adverse effects
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / metabolism
  • Enzyme Inhibitors / pharmacology*
  • Enzyme Inhibitors / therapeutic use
  • Enzyme Inhibitors / toxicity
  • Humans
  • IMP Dehydrogenase / antagonists & inhibitors*
  • Neoplasms / drug therapy*
  • Ribavirin / adverse effects
  • Ribavirin / analogs & derivatives*
  • Ribavirin / chemical synthesis
  • Ribavirin / metabolism
  • Ribavirin / pharmacology*
  • Ribavirin / therapeutic use
  • Ribavirin / toxicity
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Drugs, Investigational
  • Enzyme Inhibitors
  • Ribavirin
  • IMP Dehydrogenase
  • tiazofurin