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

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 = ...

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Bibliographic Details
Published in:Pediatric blood & cancer 2019-05, Vol.66 (5), p.e27618-n/a
Main Authors: Ramsey, Laura B., Mizuno, Tomoyuki, Vinks, Alexander A., O'Brien, Maureen M.
Format: Article
Language:English
Subjects:
Acute lymphoblastic leukemia
Adolescent
Adult
Antineoplastic Combined Chemotherapy Protocols - pharmacokinetics
Antineoplastic Combined Chemotherapy Protocols - therapeutic use
Child
Child, Preschool
dasatinib
Dasatinib - administration & dosage
Enzyme inhibitors
Female
Follow-Up Studies
glucarpidase
Hematology
Humans
Imatinib
Infant
Leukemia
Lymphatic leukemia
Male
Metabolic Clearance Rate
Methotrexate
Methotrexate - administration & dosage
Oncology
Pediatrics
pharmacokinetics
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Prognosis
Protein-tyrosine kinase
Targeted cancer therapy
Tissue Distribution
Young Adult
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Summary: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.
ISSN:1545-5009
1545-5017
DOI:10.1002/pbc.27618