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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
8
|
| pubmed:dateCreated |
1993-11-8
|
| pubmed:abstractText |
Fluorouracil remains the single most active chemotherapy agent in colorectal cancer. One of its principal mechanisms of action is inhibition of the enzyme thymidylate synthase (TS), a central enzymatic step in de novo pyrimidine synthesis. Leucovorin, which is metabolized intracellularly to polyglutamated 5,10-methylenetetrahydrofolate, modulates the cellular cytotoxicity of fluorouracil by increasing TS inhibition in vitro and in vivo. Leucovorin modulation of fluorouracil has been studied in preclinical systems and in a large number of clinical trials using various doses and schedules of both drugs. The collective data support the use of continuous infusion or repetitive low-dose schedules of leucovorin. Furthermore, these schedules appear to be less dependent on the leucovorin dose to achieve maximal clinical efficacy than does intermittent single bolus therapy. These schedules appear to be the most effective in the generation of the higher polyglutamates of 5,10-methylenetetrahydrofolate, the most efficient intracellular folate metabolite for ternary complex formation and TS inhibition.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
Aug
|
| pubmed:issn |
0890-9091
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
7
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
63-72; discussion 75-6
|
| pubmed:dateRevised |
2005-11-16
|
| pubmed:meshHeading | |
| pubmed:year |
1993
|
| pubmed:articleTitle |
Leucovorin modulation of fluorouracil.
|
| pubmed:affiliation |
NCI-Navy Medical Oncology Branch, National Cancer Institute, Bethesda, Maryland.
|
| pubmed:publicationType |
Journal Article,
Review
|