Methotrexate area under the curve is an important outcome predictor in patients with primary CNS lymphoma: A pharmacokinetic-pharmacodynamic analysis from the IELSG no. 20 trial.
Br J Cancer
; 102(4): 673-7, 2010 Feb 16.
Article
em En
| MEDLINE
| ID: mdl-20125159
ABSTRACT
BACKGROUND:
This analysis was initiated to define the predictive value of the area under the curve of high-dose methotrexate (AUC(HD-MTX)) in patients with primary central nervous system lymphoma (PCNSL). PATIENTS ANDMETHODS:
We included 55 patients with PCNSL and available pharmacokinetic (PK) data from the International Extranodal Lymphoma Study Group (IELSG) no. 20 trial, randomised to HD-MTX (n=30) or HD-MTX and high-dose cytarabine (HD-AraC) (n=25). Individual AUC(HD-MTX) from population PK analysis was tested on drug toxicity and clinical outcome using multivariate logistic regression analysis and Cox hazards modelling.RESULTS:
AUC(HD-MTX), the IELSG score and treatment group were significant predictors for treatment response (complete or partial) in the adjusted model. The AUC(HD-MTX) did not predict toxicity, with the exception of liver toxicity and neutropaenia. A high AUC(HD-MTX) was associated with better event-free survival (EFS) (P=0.01) and overall survival (OAS) (P=0.02). Both the AUC(HD-MTX) and the IELSG score were significant predictors of EFS and OAS in the adjusted model, with a hazard ratio of 0.82 and 0.73, respectively, per 100 micromol l(-1) h(-1) increase in AUC(HD-MTX).CONCLUSIONS:
Individualised dosing of HD-MTX might have the potential to improve clinical outcome in patients with PCNSL, even when administered concurrently with HD-AraC. In the future, this could be carried out by using first-cycle PK modelling with determination of potential dose adaptations for later cycles using Bayesian analysis.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Metotrexato
/
Neoplasias do Sistema Nervoso Central
/
Linfoma
Tipo de estudo:
Clinical_trials
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Female
/
Humans
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Male
/
Middle aged
Idioma:
En
Revista:
Br J Cancer
Ano de publicação:
2010
Tipo de documento:
Article
País de afiliação:
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