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28.11.2018 | Original Article

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

Zeitschrift:
Cancer Chemotherapy and Pharmacology
Autoren:
Jennifer H. Foster, Patrick A. Thompson, M. Brooke Bernhardt, Judith F. Margolin, Susan G. Hilsenbeck, Eunji Jo, Deborah A. Marquez-Do, Michael E. Scheurer, Eric S. Schafer
Wichtige Hinweise

Electronic supplementary material

The online version of this article (https://​doi.​org/​10.​1007/​s00280-018-3733-2) contains supplementary material, which is available to authorized users.

Abstract

Purpose

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.

Methods

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.

Results

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 < 80 ml/min/1.73 m2. 107/110 (97.2%) of methotrexate levels were drawn properly and 100% of algorithm dosing instructions were performed correctly at the bedside. Thirty-five (64.8%) of all cycles and 24 of 33 (72.7%) cycles that required a dose-adjustment had an end 24-h methotrexate level (Cpss) within our goal range of 65 ± 15 µM with only 3 (5.6%) resulting in Cpss higher than goal. Grade 3/4 toxicities were rare; no patients developed > Grade 1 acute kidney injury.

Conclusion

This algorithm is a simple, safe and effective method for individualizing HDMTX in pediatric patients with ALL.

Clinicaltrials.gov Registry

NCT02076997.

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Zusatzmaterial
Supplementary material 1 (DOCX 421 KB)
280_2018_3733_MOESM1_ESM.docx
Literatur
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