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Cancer Chemotherapy and Pharmacology
Published in: Cancer Chemotherapy and Pharmacology 1/2015

01-01-2015 | Original Article

Delayed methotrexate excretion in infants and young children with primary central nervous system tumors and postoperative fluid collections

Authors: Karen D. Wright, John C. Panetta, Arzu Onar-Thomas, Wilburn E. Reddick, Zoltan Patay, Ibrahim Qaddoumi, Alberto Broniscer, Giles Robinson, Frederick A. Boop, Paul Klimo Jr., Deborah Ward, Amar Gajjar, Clinton F. Stewart

Published in: Cancer Chemotherapy and Pharmacology | Issue 1/2015

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Abstract

Purpose

High-dose methotrexate (HD-MTX) has been used to treat children with central nervous system tumors. Accumulation of MTX within pleural, peritoneal, or cardiac effusions has led to delayed excretion and increased risk of systemic toxicity. This retrospective study analyzed the association of intracranial post-resection fluid collections with MTX plasma disposition in infants and young children with brain tumors.

Methods

Brain MRI findings were analyzed for postoperative intracranial fluid collections in 75 pediatric patients treated with HD-MTX and for whom serial MTX plasma concentrations (MTX) were collected. Delayed plasma excretion was defined as (MTX) ≥1 μM at 42 hours (h). Leucovorin was administered at 42 h and then every 6 h until (MTX) <0.1 μM. Population and individual MTX pharmacokinetic parameters were estimated by nonlinear mixed-effects modeling.

Results

Fifty-eight patients had intracranial fluid collections present. Population average (inter-individual variation) MTX clearance was 96.0 ml/min/m2 (41.1 CV %) and increased with age. Of the patients with intracranial fluid collections, 24 had delayed excretion; only 2 of the 17 without fluid collections (P < 0.04) had delayed excretion. Eleven patients had grade 3 or 4 toxicities attributed to HD-MTX. No significant difference was observed in intracranial fluid collection, total leucovorin dosing, or hydration fluids between those with and without toxicity.

Conclusions

Although an intracranial fluid collection is associated with delayed MTX excretion, HD-MTX can be safely administered with monitoring of infants and young children with intracranial fluid collections. Infants younger than 1 year may need additional monitoring to avoid toxicity.
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Metadata
Title
Delayed methotrexate excretion in infants and young children with primary central nervous system tumors and postoperative fluid collections
Authors
Karen D. Wright
John C. Panetta
Arzu Onar-Thomas
Wilburn E. Reddick
Zoltan Patay
Ibrahim Qaddoumi
Alberto Broniscer
Giles Robinson
Frederick A. Boop
Paul Klimo Jr.
Deborah Ward
Amar Gajjar
Clinton F. Stewart
Publication date
01-01-2015
Publisher
Springer Berlin Heidelberg
Published in
Cancer Chemotherapy and Pharmacology / Issue 1/2015
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI
https://doi.org/10.1007/s00280-014-2614-6

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