Improving 5-FU with A Novel Dihydropyrimidine Dehydrogenase Inactivator

Research output: Contribution to journalArticle

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Abstract

GW776C85 is a new drug that has been shown to be an effective inactivator of dihydropyrimidine dehydrogenase (DPD). Preclinical studies demonstrated that administration of GW776C85 with 5-fluorouracil (5-FU) resulted in several desirable pharmacologic effects. Initial clinical data on 5-FU combined with GW776C85 suggest potentially increased antitumor activity in at least some malignancies with tolerable toxicity, as we;; as several distinct economic and quality-of-life advantages including the following: (1) The possibility of administering 5-FU as an oral drug due to excellent bioavailability of 5-FU following inactivation of DPD; (2) a cost-effective alternative to continuous or protracted infusion of 5-FU without the need for hospitalization or surgical placement of an intravenous access and availability of an ambulatory pump; and (3) potential for less interpatient variation of 5-FU toxicity (eg, in host tissues, such as bone marrow and gastrointestianl mucosa cells) due to inactivation of DPD in essentially all patients treated, permitting better 5-FU dosing guidelines. Finally, because tumors may theoretically become resistant to 5-FU by increased levels of DPD, the use of GW776C85 to inactivate DPD may provide a potential means by which tumor resistance can be reversed.

Original languageEnglish (US)
Pages (from-to)51-56
Number of pages6
JournalOncology
Volume12
Issue number3 SUPPL. 4
StatePublished - Dec 1 1998

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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