5-Fluorouracil: forty-plus and still ticking. A review of its preclinical and clinical development

5-Fluorouracil (5-FU) and 5-fluoro-2'-deoxyuridine (FdUrd) are pyrimidine analogs that have been part of the therapeutic armamentarium for a variety of solid tumors for over forty years. 5-FU has customarily required intravenous administration due to poor and erratic oral bioavailability, while...

Full description

Saved in:
Bibliographic Details
Published in:Investigational new drugs 2000-11, Vol.18 (4), p.299-313
Main Author: Grem, J L
Format: Article
Language:English
Subjects:
Animals
Antimetabolites, Antineoplastic - metabolism
Antimetabolites, Antineoplastic - pharmacology
Antimetabolites, Antineoplastic - toxicity
Apoptosis
Cancer
Clinical Trials as Topic
Cytotoxicity
DNA repair
Enzymes
Fluorouracil - metabolism
Fluorouracil - pharmacology
Fluorouracil - toxicity
Humans
Kinases
Metabolism
Metabolites
Pharmacology
RNA polymerase
Tumors
Vitamin B
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:5-Fluorouracil (5-FU) and 5-fluoro-2'-deoxyuridine (FdUrd) are pyrimidine analogs that have been part of the therapeutic armamentarium for a variety of solid tumors for over forty years. 5-FU has customarily required intravenous administration due to poor and erratic oral bioavailability, while FdUrd has generally been employed for regional administration to the liver or the peritoneal cavity. A great deal of knowledge has been gained concerning the cellular pharmacology and mechanism of action of 5-FU since it was first synthesized in the late 1950's. A more thorough understanding of the factors influencing the metabolic activation of 5-FU and its cellular effects has generated considerable interest in combining it with both modulatory agents such as leucovorin and methotrexate that enhance its metabolism or cytotoxic effects. In addition, 5-FU has also been employed to enhance the therapeutic activity of other antineoplastic agents or modalities such as cisplatin and ionizing radiation with which it can synergize. Appreciation of the clinical pharmacology of 5-FU and FdUrd have led to a variety of schedules that are clinically useful. The preclinical and clinical pharmacology of 5-FU is reviewed to provide a basis for exploring the novel approaches to permit oral administration of 5-FU or its prodrugs that will be described in other articles in this issue.
ISSN:0167-6997
1573-0646
DOI:10.1023/a:1006416410198