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Int J Clin Oncol. 2018 Oct;23(5):980-988. doi: 10.1007/s10147-018-1300-9. Epub 2018 May 29.

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.

Author information

1
Department of Hematology, Fujita Health University School of Medicine, Toyoake, Japan. mizuta@spacelan.ne.jp.
2
Hematology and Immunology, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Kahoku-gun, Ishikawa, 920-0293, Japan. mizuta@spacelan.ne.jp.
3
Department of Hematology and Oncology, Anjo Kosei Hospital, Anjo, Japan.
4
Department of Hematology, Graduate School of Medicine, Gifu University, Gifu, Japan.
5
Department of Clinical Pharmaceutics, Doshisha Women's College of Liberal Arts, Kyoto, Japan.
6
Department of Hematology, Gifu Municipal Hospital, Gifu, Japan.
7
Department of Hematology, Daido Hospital, Nagoya, Japan.
8
Department of Hematology and Oncology, JA Aichi Konan Kosei Hospital, Konan, Japan.
9
Department of Medical Statistics, Faculty of Medicine, Toho University, Tokyo, Japan.
10
Department of Biomedical Statistics and Bioinformatics, Kyoto University Graduate School of Medicine, Kyoto, Japan.
11
Tokai Central Hospital, Kagamigahara, Japan.
12
Department of Hematology, Fujita Health University School of Medicine, Toyoake, Japan.

Abstract

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.

KEYWORDS:

Chronic myeloid leukemia; Dasatinib; Individualized dasatinib therapy; Plasma concentration; Treatment adherence

PMID:
29845477
PMCID:
PMC6154123
DOI:
10.1007/s10147-018-1300-9
[Indexed for MEDLINE]
Free PMC Article

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