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A prospective study of a simple algorithm to individually dose high-dose methotrexate for children with leukemia at risk for methotrexate toxicities

Authors :
Eric S. Schafer
Susan G. Hilsenbeck
Judith F. Margolin
Jennifer Foster
Michael E. Scheurer
Patrick A. Thompson
Deborah Marquez-Do
Eunji Jo
M. Brooke Bernhardt
Source :
Cancer Chemotherapy and Pharmacology. 83:349-360
Publication Year :
2018
Publisher :
Springer Science and Business Media LLC, 2018.

Abstract

High-dose methotrexate (HDMTX) is critical to the successful treatment of pediatric acute lymphoblastic leukemia (ALL) but can cause significant toxicities. This study prospectively evaluated the effectiveness of a fixed algorithm which requires no real-time pharmacokinetic modeling and no previous patient exposure to HDMTX, to individualize HDMTX dosing for at-risk patients with the aim of avoiding methotrexate-related toxicities. We developed a simple algorithm to individualize HDMTX infusions with 0–2 rate adjustments based on methotrexate levels during the infusion. This was a prospective, open-label, study; eligible patients were identified and referred by their oncologist. Fifty-four evaluable cycles of HDMTX (5 g/m2 over 24 h) were administered to 22 patients. Blood samples were obtained in 21 patients to examine single nucleotide polymorphisms (SNPs) related to methotrexate disposition. Twelve (54.5%) subjects had a history of previous HDMTX toxicities including seven (31.8%) who previously required glucarpidase rescue and seven (31.8%) with an entry glomerular filtration rate Grade 1 acute kidney injury. This algorithm is a simple, safe and effective method for individualizing HDMTX in pediatric patients with ALL. NCT02076997.

Details

ISSN :
14320843 and 03445704
Volume :
83
Database :
OpenAIRE
Journal :
Cancer Chemotherapy and Pharmacology
Accession number :
edsair.doi.dedup.....bfb45e6bd75606bb73f851d3b76330a4