A Higher Dose of Dasatinib May Increase the Possibility of Crossing the Blood-brain Barrier in the Treatment of Patients With Philadelphia Chromosome-positive Acute Lymphoblastic Leukemia.

Abstract

PURPOSE:

Dasatinib is a second-generation tyrosine kinase inhibitor with higher central nervous system (CNS) penetration compared with imatinib and nilotinib in in vitro studies. However, limited clinical data are available regarding the dosage and CNS penetration of dasatinib. The purpose of this study was to investigate the actual ability of dasatinib to cross the blood-brain barrier in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL).

METHODS:

Plasma and cerebrospinal fluid (CSF) samples collected from Ph+ ALL patients treated with dasatinib were analyzed by using an LC-MS/MS assay.

FINDINGS:

Orally administered dasatinib 100 mg once daily was well absorbed by the patient but penetrated poorly into the CSF. The use of a higher drug dosage (140 mg/d) may increase systemic drug exposure and enhance the penetration of dasatinib into the CSF.

IMPLICATIONS:

Based on this study, the use of a higher dosage of dasatinib (140 mg/d) is recommended in patients at high risk of CNS relapse or patients who need treatment for CNS leukemia. ClinicalTrials.gov identifier: NCT02523976.

• Authors: Xiaoyuan Gong, Le Li, Hui Wei, Bingcheng Liu, Chunlin Zhou, Guangji Zhang, Kaiqi Liu, Dong Lin, Benfa Gong, Shuning Wei, Yan Li, Yingchang Mi, Ying Wang, Jianxiang Wang
• Journal: Clinical therapeutics (Clin Ther) Vol. 43 Issue 7 Pg. 1265-1271.e1 (07 2021) ISSN: 1879-114X [Electronic] United States
• PMID: 34120773 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 Elsevier Inc. All rights reserved.

Chemical References

• Protein Kinase Inhibitors
• Dasatinib

Topics

• Blood-Brain Barrier
• Chromatography, Liquid
• Dasatinib
• Humans
• Philadelphia Chromosome
• Precursor Cell Lymphoblastic Leukemia-Lymphoma (drug therapy)
• Protein Kinase Inhibitors
• Tandem Mass Spectrometry