Journal article
Biochemical Rationale for the 5-Fluorouracil Leucovorin Combination and Update of Clinical Experience
Journal of chemotherapy (Florence), Vol.2(sup1), pp.5-11
02/01/1990
DOI: 10.1080/1120009X.1990.11738998
PMID: 2195138
Abstract
Although 5-fluorouracil has been the drug of choice for the treatment of patients with advanced adenocarcinoma of the colon, the reported response rate does not exceed 20% with a median survival time less than 9 months. Mechanisms of sensitivity to this agent include: 1) inhibition of thymidylate synthase by FdUMP, the active metabolite of 5-fluorouracil; 2) incorporation of FUTP into cellular RNA; and 3) incorporation of FdUTP into cellular DNA. Recent laboratory preclinical results suggest that the major site of action of 5-fluorouracil when combined with 5-formyltetrahydrofolate (folinic acid, leucovorin) is thymidylate synthase resulting in pronounced and prolonged inhibition of DNA synthesis. This effect is primarily due to the stabilization of FdUMP binding to thymidylate synthase by the reduced folate cofactor, N5, N10-methylenetetrahydrofolate.
In this paper, the rationale for the modulation of 5-fluorouracil by leucovorin, the clinical pharmacology and the clinical experience of this combination will be reviewed.
Details
- Title: Subtitle
- Biochemical Rationale for the 5-Fluorouracil Leucovorin Combination and Update of Clinical Experience
- Creators
- Y.M. Rustum - Grace Cancer Drug Center, Roswell Park Memorial Institute
- Resource Type
- Journal article
- Publication Details
- Journal of chemotherapy (Florence), Vol.2(sup1), pp.5-11
- Publisher
- Taylor & Francis
- DOI
- 10.1080/1120009X.1990.11738998
- PMID
- 2195138
- ISSN
- 1120-009X
- eISSN
- 1973-9478
- Language
- English
- Date published
- 02/01/1990
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984359927302771
Metrics
22 Record Views