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

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

Research output: Contribution to journalArticle

6 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)27-35
Number of pages9
JournalCancer Chemotherapy and Pharmacology
Volume75
Issue number1
DOIs
StatePublished - Jan 1 2015

Fingerprint

Central Nervous System Neoplasms
Neurology
Methotrexate
Tumors
Fluids
Leucovorin
Toxicity
Brain Neoplasms
Population
Plasmas
Retrospective Studies
Pharmacokinetics
Brain
Pediatrics
Monitoring
Hydration
Magnetic resonance imaging
Association reactions

All Science Journal Classification (ASJC) codes

  • Oncology
  • Toxicology
  • Pharmacology
  • Cancer Research
  • Pharmacology (medical)

Cite this

Delayed methotrexate excretion in infants and young children with primary central nervous system tumors and postoperative fluid collections. / Wright, Karen D.; Panetta, John C.; Onar-Thomas, Arzu; Reddick, Wilburn E.; Patay, Zoltan; Qaddoumi, Ibrahim; Broniscer, Alberto; Robinson, Giles; Boop, Frederick; Klimo, Paul; Ward, Deborah; Gajjar, Amar; Stewart, Clinton F.

In: Cancer Chemotherapy and Pharmacology, Vol. 75, No. 1, 01.01.2015, p. 27-35.

Research output: Contribution to journalArticle

Wright, KD, Panetta, JC, Onar-Thomas, A, Reddick, WE, Patay, Z, Qaddoumi, I, Broniscer, A, Robinson, G, Boop, F, Klimo, P, Ward, D, Gajjar, A & Stewart, CF 2015, 'Delayed methotrexate excretion in infants and young children with primary central nervous system tumors and postoperative fluid collections', Cancer Chemotherapy and Pharmacology, vol. 75, no. 1, pp. 27-35. https://doi.org/10.1007/s00280-014-2614-6
Wright, Karen D. ; Panetta, John C. ; Onar-Thomas, Arzu ; Reddick, Wilburn E. ; Patay, Zoltan ; Qaddoumi, Ibrahim ; Broniscer, Alberto ; Robinson, Giles ; Boop, Frederick ; Klimo, Paul ; Ward, Deborah ; Gajjar, Amar ; Stewart, Clinton F. / Delayed methotrexate excretion in infants and young children with primary central nervous system tumors and postoperative fluid collections. In: Cancer Chemotherapy and Pharmacology. 2015 ; Vol. 75, No. 1. pp. 27-35.
@article{55feee7b118447859e4e064ba23b2860,
title = "Delayed methotrexate excretion in infants and young children with primary central nervous system tumors and postoperative fluid collections",
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.",
author = "Wright, {Karen D.} and Panetta, {John C.} and Arzu Onar-Thomas and Reddick, {Wilburn E.} and Zoltan Patay and Ibrahim Qaddoumi and Alberto Broniscer and Giles Robinson and Frederick Boop and Paul Klimo and Deborah Ward and Amar Gajjar and Stewart, {Clinton F.}",
year = "2015",
month = "1",
day = "1",
doi = "10.1007/s00280-014-2614-6",
language = "English (US)",
volume = "75",
pages = "27--35",
journal = "Cancer Chemotherapy and Pharmacology",
issn = "0344-5704",
publisher = "Springer Verlag",
number = "1",

}

TY - JOUR

T1 - Delayed methotrexate excretion in infants and young children with primary central nervous system tumors and postoperative fluid collections

AU - Wright, Karen D.

AU - Panetta, John C.

AU - Onar-Thomas, Arzu

AU - Reddick, Wilburn E.

AU - Patay, Zoltan

AU - Qaddoumi, Ibrahim

AU - Broniscer, Alberto

AU - Robinson, Giles

AU - Boop, Frederick

AU - Klimo, Paul

AU - Ward, Deborah

AU - Gajjar, Amar

AU - Stewart, Clinton F.

PY - 2015/1/1

Y1 - 2015/1/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84925498175&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84925498175&partnerID=8YFLogxK

U2 - 10.1007/s00280-014-2614-6

DO - 10.1007/s00280-014-2614-6

M3 - Article

VL - 75

SP - 27

EP - 35

JO - Cancer Chemotherapy and Pharmacology

JF - Cancer Chemotherapy and Pharmacology

SN - 0344-5704

IS - 1

ER -