ArticleCancer chemotherapy and pharmacology2015
Delayed methotrexate excretion in infants and young children with primary central nervous system tumors and postoperative fluid collections.
Article in Cancer chemotherapy and pharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 4 of them syntheses that pooled it.
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14 citing papers in PubMed, 4 syntheses or guidelines pooled it, 36 citations in OpenAlex.
- Population pharmacokinetic analyses of methotrexate in pediatric patients: a systematic review.European journal of clinical pharmacology · 2024Pooled it
- Extracorporeal Treatment for Methotrexate Poisoning: Systematic Review and Recommendations from the EXTRIP Workgroup.Clinical journal of the American Society of Nephrology : CJASN · 2022Pooled it
- Clinical pharmacology of cytotoxic drugs in neonates and infants: Providing evidence-based dosing guidance.European journal of cancer (Oxford, England : 1990) · 2022Pooled it
- A Systematic Review of Population Pharmacokinetic Models of Methotrexate.European journal of drug metabolism and pharmacokinetics · 2022Pooled it
- Population Pharmacokinetics and Covariate Analysis of Methotrexate in Pediatric Acute Lymphoblastic Leukemia.Drug design, development and therapy · 2025Article
- Population pharmacokinetics of high-dose methotrexate in patients with primary central nervous system lymphoma.Frontiers in pharmacology · 2025Article
- An interactive dose optimizer based on population pharmacokinetic study to guide dosing of methotrexate in Chinese patients with osteosarcoma.Cancer chemotherapy and pharmacology · 2024Article
- Understanding hemoglobin contribution to high-dose methotrexate disposition-population pharmacokinetics in pediatric patients with hematological malignancies.European journal of clinical pharmacology · 2024Article
- Population pharmacokinetics of methotrexate and 7-hydroxymethotrexate and delayed excretion in infants and young children with brain tumors.European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences · 2024Article
- Risk factors for delayed elimination of high-dose methotrexate in childhood acute lymphoblastic leukemia and lymphoma.International journal of hematology · 2021Article
- Preventing and Managing Toxicities of High-Dose Methotrexate.The oncologist · 2016Review
- Determination of Methotrexate, 7-Hydroxymethotrexate, and 2,4-Diamino-NJournal of liquid chromatography & related technologies · 2016Article
- Response to: comment on "Delayed methotrexate excretion in infants and young children with primary central nervous system tumors and postoperative fluid collections".Cancer chemotherapy and pharmacology · 2015Article
- Outcome and molecular analysis of young children with choroid plexus carcinoma treated with non-myeloablative therapy: results from the SJYC07 trial.Neuro-oncology advancesArticle
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13 authors at 2 institutions in 1 country.
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Abstract
purposeHigh-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.
methodsBrain 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.
resultsFifty-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.
conclusionsAlthough 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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