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Cancer Chemotherapy and Pharmacology
Published in: Cancer Chemotherapy and Pharmacology 6/2014

01-12-2014 | Clinical Trial Report

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

Authors: V. Gotta, N. Widmer, L. A. Decosterd, Y. Chalandon, D. Heim, M. Gregor, R. Benz, L. Leoncini-Franscini, G. M. Baerlocher, M. A. Duchosal, C. Csajka, T. Buclin

Published in: Cancer Chemotherapy and Pharmacology | Issue 6/2014

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Abstract

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.
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Metadata
Title
Clinical usefulness of therapeutic concentration monitoring for imatinib dosage individualization: results from a randomized controlled trial
Authors
V. Gotta
N. Widmer
L. A. Decosterd
Y. Chalandon
D. Heim
M. Gregor
R. Benz
L. Leoncini-Franscini
G. M. Baerlocher
M. A. Duchosal
C. Csajka
T. Buclin
Publication date
01-12-2014
Publisher
Springer Berlin Heidelberg
Published in
Cancer Chemotherapy and Pharmacology / Issue 6/2014
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI
https://doi.org/10.1007/s00280-014-2599-1

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