Large-scale imatinib dose-concentration-effect study in CML patients under routine care conditions.


Autoria(s): Gotta V.; Bouchet S.; Widmer N.; Schuld P.; Decosterd L.A.; Buclin T.; Mahon F.X.; Csajka C.; Molimard M.
Data(s)

2014

Resumo

This observational study analyzed imatinib pharmacokinetics and response in 2478 chronic myeloid leukemia (CML) patients. Data were obtained through centralized therapeutic drug monitoring (TDM) at median treatment duration of ≥2 years. First, individual initial trough concentrations under 400mg/day imatinib starting dose were estimated. Second, their correlation (C^min(400mg)) with reported treatment response was verified. Low imatinib levels were predicted in young male patients and those receiving P-gp/CYP3A4 inducers. These patients had also lower response rates (7% lower 18-months MMR in male, 17% lower 1-year CCyR in young patients, Kaplan-Meier estimates). Time-point independent multivariate regression confirmed a correlation of individual C^min(400mg) with response and adverse events. Possibly due to confounding factors (e.g. dose modifications, patient selection bias), the relationship seemed however flatter than previously reported from prospective controlled studies. Nonetheless, these observational results strongly suggest that a subgroup of patients could benefit from early dosage optimization assisted by TDM, because of lower imatinib concentrations and lower response rates.

Identificador

http://serval.unil.ch/?id=serval:BIB_0F6749D7DFF3

isbn:1873-5835 (Electronic)

pmid:24844604

doi:10.1016/j.leukres.2014.03.023

isiid:000339339400008

Idioma(s)

en

Fonte

Leukemia Research, vol. 38, no. 7, pp. 764-772

Tipo

info:eu-repo/semantics/article

article