Relationships between imatinib plasma levels and efficacy

Détails

ID Serval
serval:BIB_04D9A704BCA5
Type
Actes de conférence (partie): contribution originale à la littérature scientifique, publiée à l'occasion de conférences scientifiques, dans un ouvrage de compte-rendu (proceedings), ou dans l'édition spéciale d'un journal reconnu (conference proceedings).
Sous-type
Abstract (résumé de présentation): article court qui reprend les éléments essentiels présentés à l'occasion d'une conférence scientifique dans un poster ou lors d'une intervention orale.
Collection
Publications
Titre
Relationships between imatinib plasma levels and efficacy
Titre de la conférence
75. Jahresversammlung der Schweizerisches Gesellschaft für Innere Medizin
Auteur(s)
Widmer N., Decosterd L.A., Leyvraz S., Duchosal M.A., Rosselet A., Debiec-Rychter M., Csajka C., Biollaz J., Buclin T.
Adresse
Basel, Schweiz, 23.-25. Mai 2007
ISBN
1424-4985
Statut éditorial
Publié
Date de publication
2007
Peer-reviewed
Oui
Volume
7
Série
Swiss Medical Forum = Forum Médical Suisse
Pages
80S
Langue
anglais
Résumé
Purpose: While imatinib has revolutionized the treatment of chronic myeloid leukaemia (CML) and gastrointestinal stromal tumors (GIST), its pharmacokinetic-pharmacodynamic relationships have been poorly studied. This study aimed to explore the issue in oncologic patients, and to evaluate the specific influence of the target genotype in a GIST subpopulation.
Patients and methods: Data from 59 patients (321 plasma samples) were collected during a previous pharmacokinetic study. Based on a population model purposely developed, individual post-hoc Bayesian estimates of pharmacokinetic parameters were derived, and used to estimate drug exposure (AUC; area under curve). Free fraction parameters were deduced from a model incorporating plasma alpha1-acid glycoprotein levels. Associations between AUC (or clearance) and therapeutic response (coded on a 3-point scale), or tolerability (4-point scale), were explored by ordered logistic regression. Influence of KIT genotype on response was also assessed in GIST patients.
Results: Total and free drug exposure correlated with the number of side effects (p < 0.005). A relationship with response was not evident in the whole patient set (with good-responders tending to receive lower doses and bad-responders higher doses). In GIST patients however, higher free drug exposure predicted better responses. A strong association was notably observed in patients harboring an exon 9 mutation or a wild type KIT, known to decrease tumor sensitivity towards imatinib (p < 0.005).
Conclusions: Our results are arguments to further evaluate the potential benefit of a therapeutic monitoring program for imatinib. Our data also suggest that stratification by genotype will be important in future trials.
Création de la notice
01/12/2010 10:57
Dernière modification de la notice
03/03/2018 13:23
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