Imatinib trough plasma levels do not correlate with the response to therapy in patients with chronic myeloid leukemia in routine clinical setting
Jazyk angličtina Země Německo Médium print-electronic
Typ dokumentu hodnotící studie, časopisecké články, práce podpořená grantem
- MeSH
- benzamidy MeSH
- biochemická analýza krve MeSH
- biomarkery farmakologické analýza krev MeSH
- chronická myeloidní leukemie krev diagnóza farmakoterapie metabolismus MeSH
- diagnostické testy rutinní MeSH
- dospělí MeSH
- imatinib mesylát MeSH
- klinické laboratorní techniky MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- piperaziny analýza krev farmakokinetika terapeutické užití MeSH
- prediktivní hodnota testů MeSH
- prognóza MeSH
- protinádorové látky analýza krev farmakokinetika terapeutické užití MeSH
- pyrimidiny analýza krev farmakokinetika terapeutické užití MeSH
- retrospektivní studie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- hodnotící studie MeSH
- práce podpořená grantem MeSH
- Názvy látek
- benzamidy MeSH
- biomarkery farmakologické MeSH
- imatinib mesylát MeSH
- piperaziny MeSH
- protinádorové látky MeSH
- pyrimidiny MeSH
Association of trough imatinib plasma levels (IPL) with cytogenetic or molecular response to treatment in patients with chronic myeloid leukemia (CML) was repeatedly reported. We analyzed their value in the routine clinical setting in 131 patients with chronic phase CML in whom imatinib was applied as first- or second-line treatment. A total of 1,118 measurements were obtained by ultra-performance liquid chromatography-tandem mass spectrometry assay in patients treated with daily dose of imatinib ranging from 100 to 800 mg. Samples were obtained from 1 to 96 h after drug ingestion. High inter (36%) and intraindividual variability (9-33%) of IPL was observed. For analysis of correlation of IPL with treatment response, two sets of samples were selected according to the European LeukemiaNet (ELN) criteria. The first set consisted of 241 samples taken 24 ± 2 h after dosing in 54 patients, and the second one consisted of 329 samples taken 24 ± 4 h after imatinib ingestion in 84 patients. In both sets, only patients treated with 400 mg imatinib once daily for at least 18 months were included. From multiple measurements in individual patients, mean IPL were used. In both sets, we were not able to demonstrate a statistically significant correlation between IPL and response to treatment according to the ELN. We believe that this was due to the differences in patients' compliance, leukemia biology, and other variables that are difficult to eliminate in the routine clinical practice. The use of IPL for prognostic estimation in CML treatment outside the clinical trials is probably limited.
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