Document Detail


Impact of UFT on tumoral TS and DPD levels in colorectal cancer.
MedLine Citation:
PMID:  11098489     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
This was an open lable, pilot translational clinical pharmacology study of a brief (7 day) course of UFT, 300 mg/m2/day, in combination with leucovorin, 90 mg/day, in six patients with newly diagnosed advanced colorectal cancer. The primary objectives of the study were to examine the impact of this treatment course on the UFT targets which are thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD). The rate of tumoral TS inhibition after the 7-day UFT treatment sequence varied from 5% up to 31%. UFT treatment induced a constant and variable decrease in tumor DPD activity ranging from 13% to 60%. UFT treatment induced a constant increase in uracil concentrations both in plasma and tumors. FT, 5-FU and the metabolite fluoro-beta-alanine (FBAL) were found in plasma and tumors at variable concentrations; the highest drug concentrations were those of FBAL in plasma. The present translational clinical study provides data related to the in vivo pharmacological effects of UFT with a description of its impact on cellular targets.
Authors:
G Bastian; J F Seitz; V Moutardier; J R Delperro; P Fargeot; J Fraisse; P Formento; M Chazard; N Renée; G Milano
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Publication Detail:
Type:  Clinical Trial; Journal Article    
Journal Detail:
Title:  Oncology (Williston Park, N.Y.)     Volume:  14     ISSN:  0890-9091     ISO Abbreviation:  Oncology (Williston Park, N.Y.)     Publication Date:  2000 Oct 
Date Detail:
Created Date:  2001-02-12     Completed Date:  2001-03-01     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8712059     Medline TA:  Oncology (Williston Park)     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  35-7     Citation Subset:  IM    
Affiliation:
Hôpital Pitié Salpétrière Paris, France.
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MeSH Terms
Descriptor/Qualifier:
Administration, Oral
Aged
Antineoplastic Combined Chemotherapy Protocols / administration & dosage,  pharmacology,  therapeutic use*
Colorectal Neoplasms / drug therapy*,  enzymology
Dihydrouracil Dehydrogenase (NADP)
Drug Administration Schedule
Drug Therapy, Combination
Female
Humans
Leucovorin / administration & dosage
Male
Middle Aged
Oxidoreductases / analysis*,  drug effects
Pilot Projects
Tegafur / administration & dosage
Thymidylate Synthase / analysis*,  drug effects
Uracil / administration & dosage
Chemical
Reg. No./Substance:
17902-23-7/Tegafur; 58-05-9/Leucovorin; 66-22-8/Uracil; 74578-38-4/1-UFT protocol; EC 1.-/Oxidoreductases; EC 1.3.1.2/Dihydrouracil Dehydrogenase (NADP); EC 2.1.1.45/Thymidylate Synthase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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