levoleucovorin and Pleural-Effusion--Malignant

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.. 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.. 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.. 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.

Topics: Antimetabolites, Antineoplastic; Ascitic Fluid; Central Nervous System Neoplasms; Child, Preschool; Cohort Studies; Combined Modality Therapy; Down-Regulation; Drainage; Female; Humans; Infant; Infant, Newborn; Leucovorin; Male; Metabolic Clearance Rate; Methotrexate; Neuroprotective Agents; Pericardial Effusion; Pleural Effusion, Malignant; Postoperative Complications; Retrospective Studies; Subdural Effusion

Topics: Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Benzamides; Chromosomes, Human, Pair 22; Chromosomes, Human, Pair 9; Cytarabine; Drug Interactions; Edema; Etoposide; Female; Humans; Imatinib Mesylate; Leucovorin; Methotrexate; Middle Aged; Piperazines; Pleural Effusion, Malignant; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma; Pyrimidines; Sodium Potassium Chloride Symporter Inhibitors; Translocation, Genetic