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Wright KD, Panetta JC, Onar-Thomas A, et al. Delayed methotrexate excretion in infants and young children with primary central nervous system tumors and postoperative fluid collections. Cancer Chemother Pharmacol. 2014;75(1):27-35doi: 10.1007/s00280-014-2614-6.
Wright, K. D., Panetta, J. C., Onar-Thomas, A., Reddick, W. E., Patay, Z., Qaddoumi, I., Broniscer, A., Robinson, G., Boop, F. A., Klimo, P., Ward, D., Gajjar, A., & Stewart, C. F. (2015). Delayed methotrexate excretion in infants and young children with primary central nervous system tumors and postoperative fluid collections. Cancer chemotherapy and pharmacology, 75(1), 27-35. https://doi.org/10.1007/s00280-014-2614-6
Wright, Karen D, et al. "Delayed methotrexate excretion in infants and young children with primary central nervous system tumors and postoperative fluid collections." Cancer chemotherapy and pharmacology vol. 75,1 (2015): 27-35. doi: https://doi.org/10.1007/s00280-014-2614-6
Wright KD, Panetta JC, Onar-Thomas A, Reddick WE, Patay Z, Qaddoumi I, Broniscer A, Robinson G, Boop FA, Klimo P, Ward D, Gajjar A, Stewart CF. Delayed methotrexate excretion in infants and young children with primary central nervous system tumors and postoperative fluid collections. Cancer Chemother Pharmacol. 2015 Jan;75(1):27-35. doi: 10.1007/s00280-014-2614-6. Epub 2014 Oct 24. PMID: 25342291; PMCID: PMC4282603.
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Cancer Chemother Pharmacol. 2015 Jan;75(1):27-35. doi: 10.1007/s00280-014-2614-6. Epub 2014 Oct 24.

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

Cancer chemotherapy and pharmacology

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, Deborah Ward, Amar Gajjar, Clinton F Stewart

Affiliations

  1. Division of Neuro-oncology, Department of Oncology, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Mail Stop 260, Memphis, TN, 38105, USA, [email protected].

PMID: 25342291 PMCID: PMC4282603 DOI: 10.1007/s00280-014-2614-6

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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