Plasma disposition of capecitabine and its metabolites 5'DFCR and 5'DFUR in a standard and dose-intensified monotherapy regimen.
Cancer Chemother Pharmacol
; 67(3): 613-9, 2011 Mar.
Article
em En
| MEDLINE
| ID: mdl-20495919
ABSTRACT
PURPOSE:
In view of a potential gain in anticancer activity in advanced colorectal cancer (ACRC), there has been considerable interest in using a higher than the approved standard dose of capecitabine (CCB) combined with oxaliplatin. This pharmacokinetic study was designed to evaluate whether CCB is metabolized at the same extent when administered as a monotherapy in two different dose regimens, comparing standard dose (CCB 1) and intensified dose (CCB 2). PATIENTS ANDMETHODS:
Seven patients suffering from ACRC received subsequently two CCB schedules In the standard schedule, 1,250 mg/m² CCB p.o. twice daily for 2 weeks was administered, after a pause of 1 week, a dose-intensified CCB 2 schedule was given 1,750 mg/m² CCB p.o. twice daily for 1 week to be followed by 1 week rest. Due to this paired cross over design a direct comparison for each single patient was feasible.RESULTS:
In both schedules, mean peak plasma concentrations of CCB occurred at about 50 min, those of metabolites shortly later (range 54-80 min). Peak plasma concentrations were about 10% (CCB, DFCR) and 40% (DFUR) higher in the CCB 2 regimen. According to the higher dose of CCB in the dose-intensified regimen (+40%), the AUC(last) values increased by 34% (CCB), 20% (DFCR) and 58% (DFUR), respectively.CONCLUSION:
The results indicate that higher doses of CCB are metabolized approximately dose-dependent compared to the standard dose. No indices for a saturation of metabolizing processes or any significant delay of elimination rate was observed. The immediate 5FU precursor DFUR was formed at a 50% higher extent (expressed as AUC(last) values) than in the standard CCB 1 schedule. From the pharmacokinetic point of view, this increased formation rate suggests clinical importance in regard to metabolic activation of CCB.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Colorretais
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Floxuridina
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Desoxicitidina
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Fluoruracila
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Antimetabólitos Antineoplásicos
Tipo de estudo:
Clinical_trials
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Prognostic_studies
Limite:
Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Cancer Chemother Pharmacol
Ano de publicação:
2011
Tipo de documento:
Article