Plasma concentrations of dasatinib have a clinical impact on the frequency of dasatinib dose reduction and interruption in chronic myeloid leukemia: an analysis of the DARIA 01 study.
Int J Clin Oncol
; 23(5): 980-988, 2018 Oct.
Article
em En
| MEDLINE
| ID: mdl-29845477
BACKGROUND: Dasatinib has shown promising anti-leukemic activity against chronic myeloid leukemia (CML). However, patients receiving dasatinib frequently require dose reductions and treatment interruptions (treatment alteration). METHODS: We prospectively analyzed the frequency and significance of treatment alteration during dasatinib therapy in patients with CML. In all patients, trough plasma concentrations of dasatinib (Cmin) at steady state were assessed on day 28 of therapy. RESULTS: 28% of patients had their doses reduced at a median of 42 days, and 25% of patients had temporarily interrupted at a median of 54 days after treatment initiation. The overall dasatinib treatment alteration-free rate at 1 year was 66%. Age was significantly correlated with Cmin on day 28 (p = 0.014), and the correlation remained significant after adjusting dasatinib dose (g), body weight (kg) (Cmin/D/W) (p = 0.026). In the univariate analysis, deep molecular response, advanced PS, higher Cmin/D/W were associated with a significantly higher risk of treatment alteration (HR 4.19, 95% CI: 1.06-16.60, p = 0.041; HR 5.26, 95% CI: 1.33-20.80, p = 0.018; and HR 10.15, 95% CI: 2.55-40.48, p = 0.001, respectively). In the multivariate analysis, advanced PS and higher Cmin/D/W were correlated with the incidence of treatment alteration (HR 4.78, 95% CI: 1.01-22.70, p = 0.049; HR 6.17, 95% CI: 1.17-32.50, respectively). CONCLUSION: Current data demonstrate that patients treated with dasatinib who displayed a high Cmin/D/W value and/or advanced PS were at a high risk for altered treatment.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Temas:
Mortalidade
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Geral
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Tipos_de_cancer
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Leucemia
Base de dados:
MEDLINE
Assunto principal:
Leucemia Mielogênica Crônica BCR-ABL Positiva
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Inibidores de Proteínas Quinases
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Dasatinibe
Tipo de estudo:
Clinical_trials
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Observational_studies
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Risk_factors_studies
Limite:
Adult
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Aged
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Aged80
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Female
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Humans
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Male
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Middle aged
País/Região como assunto:
Asia
Idioma:
En
Revista:
Int J Clin Oncol
Assunto da revista:
NEOPLASIAS
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Japão