Relationships between imatinib plasma levels and efficacy

Details

Serval ID
serval:BIB_04D9A704BCA5
Type
Inproceedings: an article in a conference proceedings.
Publication sub-type
Abstract (Abstract): shot summary in a article that contain essentials elements presented during a scientific conference, lecture or from a poster.
Collection
Publications
Institution
Title
Relationships between imatinib plasma levels and efficacy
Title of the conference
75. Jahresversammlung der Schweizerisches Gesellschaft für Innere Medizin
Author(s)
Widmer N., Decosterd L.A., Leyvraz S., Duchosal M.A., Rosselet A., Debiec-Rychter M., Csajka C., Biollaz J., Buclin T.
Address
Basel, Schweiz, 23.-25. Mai 2007
ISBN
1424-4985
Publication state
Published
Issued date
2007
Peer-reviewed
Oui
Volume
7
Series
Swiss Medical Forum = Forum Médical Suisse
Pages
80S
Language
english
Abstract
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.
Create date
01/12/2010 9:57
Last modification date
20/08/2019 12:26
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