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

International Journal of Clinical Oncology
Shuichi MizutaNobuhiko Emi

Abstract

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). 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. 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 c...Continue Reading

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Citations

Mar 1, 2020·Clinical Pharmacokinetics·Dominique LevêqueShanti Natarajan-Amé
Mar 11, 2020·International Journal of Hematology·Jinichi MoriNaoto Takahashi
Jun 15, 2019·Current Hematologic Malignancy Reports·M Copland
Nov 10, 2020·European Journal of Clinical Pharmacology·Anna Mueller-SchoellCharlotte Kloft
Apr 2, 2021·International Journal of Nanomedicine·Hairong WangJianchun Li

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