Clinical usefulness of therapeutic concentration monitoring for imatinib dosage individualization: results from a randomized controlled trial.

Détails

ID Serval
serval:BIB_8EFC5835C440
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Clinical usefulness of therapeutic concentration monitoring for imatinib dosage individualization: results from a randomized controlled trial.
Périodique
Cancer Chemotherapy and Pharmacology
Auteur(s)
Gotta V., Widmer N., Decosterd L.A., Chalandon Y., Heim D., Gregor M., Benz R., Leoncini-Franscini L., Baerlocher G.M., Duchosal M.A., Csajka C., Buclin T.
ISSN
1432-0843 (Electronic)
ISSN-L
0344-5704
Statut éditorial
Publié
Date de publication
2014
Peer-reviewed
Oui
Volume
74
Numéro
6
Pages
1307-1319
Langue
anglais
Notes
Publication types: Journal Article
Résumé
PURPOSE: This study assessed whether a cycle of "routine" therapeutic drug monitoring (TDM) for imatinib dosage individualization, targeting an imatinib trough plasma concentration (C min) of 1,000 ng/ml (tolerance: 750-1,500 ng/ml), could improve clinical outcomes in chronic myelogenous leukemia (CML) patients, compared with TDM use only in case of problems ("rescue" TDM).
METHODS: Imatinib concentration monitoring evaluation was a multicenter randomized controlled trial including adult patients in chronic or accelerated phase CML receiving imatinib since less than 5 years. Patients were allocated 1:1 to "routine TDM" or "rescue TDM." The primary endpoint was a combined outcome (failure- and toxicity-free survival with continuation on imatinib) over 1-year follow-up, analyzed in intention-to-treat (ISRCTN31181395).
RESULTS: Among 56 patients (55 evaluable), 14/27 (52 %) receiving "routine TDM" remained event-free versus 16/28 (57 %) "rescue TDM" controls (P = 0.69). In the "routine TDM" arm, dosage recommendations were correctly adopted in 14 patients (median C min: 895 ng/ml), who had fewer unfavorable events (28 %) than the 13 not receiving the advised dosage (77 %; P = 0.03; median C min: 648 ng/ml).
CONCLUSIONS: This first target concentration intervention trial could not formally demonstrate a benefit of "routine TDM" because of small patient number and surprisingly limited prescriber's adherence to dosage recommendations. Favorable outcomes were, however, found in patients actually elected for target dosing. This study thus shows first prospective indication for TDM being a useful tool to guide drug dosage and shift decisions. The study design and analysis provide an interesting paradigm for future randomized TDM trials on targeted anticancer agents.
Pubmed
Web of science
Création de la notice
27/12/2014 10:17
Dernière modification de la notice
03/03/2018 19:20
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