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Delayed methotrexate clearance in patients with acute lymphoblastic leukemia concurrently receiving dasatinib.

Authors
  • Ramsey, Laura B1, 2, 3
  • Mizuno, Tomoyuki2, 3
  • Vinks, Alexander A1, 2, 3
  • O'Brien, Maureen M3, 4
  • 1 Division of Research in Patient Services, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
  • 2 Division of Clinical Pharmacology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
  • 3 Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio.
  • 4 Division of Oncology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
Type
Published Article
Journal
Pediatric Blood & Cancer
Publisher
Wiley (John Wiley & Sons)
Publication Date
May 01, 2019
Volume
66
Issue
5
Identifiers
DOI: 10.1002/pbc.27618
PMID: 30677213
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

We aimed to determine whether patients receiving dasatinib or imatinib concurrently with high-dose methotrexate (HDMTX) had slower methotrexate clearance than patients not receiving a tyrosine kinase inhibitor (TKI) during the HDMTX infusion. Patients concurrently receiving dasatinib and HDMTX (N = 7) had significantly slower MTX clearance (P = 0.008) than patients not receiving a TKI (N = 111). Two patients receiving a TKI during a HDMTX infusion required glucarpidase. In vitro studies showed that dasatinib significantly inhibited methotrexate uptake by SLCO1B1-expressing cells (P = 0.009). There may be an interaction between dasatinib and HDMTX, mediated by the transporter SLCO1B1, that causes a delay in MTX clearance. © 2019 Wiley Periodicals, Inc.

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