title: Toxicity following concurrent intrathecal and moderate-dose intravenous methotrexate.
abstract: To evaluate factors predisposing children with non-Hodgkin's lymphoma to toxicity from moderate dose methotrexate (MTX) (300 mg/m2 per 4 hours), we reviewed the medical records of 15 patients treated at our institution according to two similar protocols. Five patients experienced hyperemesis and/or severe mucositis. In two of these patients, pharmacokinetic analysis demonstrated delayed terminal excretion of methotrexate with a half-life of 3-3.5 days, compared to a previously reported t1/2 of 8-15 hours in subjects with normal clearance. All affected patients were large (body surface area 1.6-1.9 m2), and MTX toxicity was seen only during courses where intravenous MTX was given concurrently with intrathecal MTX. Four patients also received simultaneous prophylactic doses of oral trimethoprim-sulfamethoxazole (trimethoprim 5 mg/kg per day). We recommend that, in protocol design, consideration be given to avoiding concurrent use of intravenous and intrathecal MTX, and possibly trimethoprim-sulfamethoxazole. Where high doses of MTX are given based on large body surface area, urine alkalinization may be indicated.
authors.affiliation: Department of Pediatrics, Children's Hospital of Pittsburgh 15213-2583.
authors.forename: J
authors.initials: J
authors.lastname: Blatt
authors.forename: D L
authors.initials: DL
authors.lastname: Howrie
authors.forename: M R
authors.initials: MR
authors.lastname: Wollman
authors.forename: C
authors.initials: C
authors.lastname: Phebus
authors.forename: J
authors.initials: J
authors.lastname: Mirro
mesh_terms: D000293:Adolescent; D001830:Body Surface Area; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007278:Injections, Spinal; D008297:Male; D008657:Metabolic Clearance Rate; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000378:metabolism; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D015662:Trimethoprim, Sulfamethoxazole Drug Combination; D008727:Methotrexate