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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
2
|
| pubmed:dateCreated |
1996-6-7
|
| pubmed:abstractText |
Leucovorin (LV) is commonly used as a modulator of 5-fluorouracil (5-FU) cytotoxicity. In patient with colon cancer, the addition of LV to 5-FU improves response rates, and in some trials has improved survival in advanced disease and in the adjuvant setting. Leucovorin is generally administered as a racemic mixture, but the isomers differ substantially in pharmacokinetics and biological activity, with 6S-LV the predominant active component. The current study was undertaken to determine the effect of 6R on the pharmacokinetics of 6S-LV, and to characterize the toxicity and antitumor effect of 5-FU when administered with 6S-LV to patients with advanced colorectal carcinoma. Thirty patients were treated with weekly 5-FU plus high dose 6S-LV. To determine the effects of 6R-LV on the pharmacokinetics of S6-LV, 20 patients were randomly assigned to receive either 250 mg/m2 6S-LV or 500 mg/m2 6R,S-LV as a 2 hour IV infusion on day -2, and the other preparation on day -1, with pharmacokinetics measured each day. The presence of 6R-LV had no effect on the AUC, Clp, Cmax, or terminal phase t1/2 of 6S-LV. The overall response rate was 40% (C.I. 23-60%). The most frequent toxicities were gastrointestinal. In this small cohort, scheduled and delivered dose intensity was positively associated with response (p = 0.05). These results show that there is no pharmacokinetic advantage to the use of 6S-LV rather than 6R,S-LV as a modulator of 5-FU.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antidotes,
http://linkedlifedata.com/resource/pubmed/chemical/Antimetabolites, Antineoplastic,
http://linkedlifedata.com/resource/pubmed/chemical/Drugs, Investigational,
http://linkedlifedata.com/resource/pubmed/chemical/Fluorouracil,
http://linkedlifedata.com/resource/pubmed/chemical/Leucovorin
|
| pubmed:status |
MEDLINE
|
| pubmed:issn |
0167-6997
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
13
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
149-55
|
| pubmed:dateRevised |
2004-11-17
|
| pubmed:meshHeading |
pubmed-meshheading:8617578-Adult,
pubmed-meshheading:8617578-Aged,
pubmed-meshheading:8617578-Antidotes,
pubmed-meshheading:8617578-Antimetabolites, Antineoplastic,
pubmed-meshheading:8617578-Carcinoma,
pubmed-meshheading:8617578-Cohort Studies,
pubmed-meshheading:8617578-Colorectal Neoplasms,
pubmed-meshheading:8617578-Digestive System,
pubmed-meshheading:8617578-Dose-Response Relationship, Drug,
pubmed-meshheading:8617578-Drug Interactions,
pubmed-meshheading:8617578-Drugs, Investigational,
pubmed-meshheading:8617578-Female,
pubmed-meshheading:8617578-Fluorouracil,
pubmed-meshheading:8617578-Humans,
pubmed-meshheading:8617578-Infusions, Intravenous,
pubmed-meshheading:8617578-Leucovorin,
pubmed-meshheading:8617578-Liver Neoplasms,
pubmed-meshheading:8617578-Male,
pubmed-meshheading:8617578-Middle Aged,
pubmed-meshheading:8617578-Reproducibility of Results,
pubmed-meshheading:8617578-Stereoisomerism,
pubmed-meshheading:8617578-Treatment Outcome
|
| pubmed:year |
1995
|
| pubmed:articleTitle |
A phase II and pharmacokinetic study of 6S-leucovorin plus 5-fluorouracil in patient with colorectal carcinoma.
|
| pubmed:affiliation |
Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
|
| pubmed:publicationType |
Journal Article,
Clinical Trial,
Randomized Controlled Trial,
Clinical Trial, Phase II
|