Toxicity following concurrent intrathecal and moderate-dose intravenous methotrexate
Blatt, J.; Howrie, D.L.; Wollman, M.R.; Phebus, C.; Mirro, J.
Leukemia 7(11): 1734-1737
1993
ISSN/ISBN: 0887-6924 PMID: 8231243 Document Number: 415603
To evaluate factors predisposing children with non-Hodgkin's lymphoma to toxicity from moderate dose methotrexate (MTX) (30O mg/m-2 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 t-1/2 of 8-15 hours in subjects with normal clearance. All affected patients were large (body surface area 1.6-1.9 m-2), 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 trimethoprimsulfamethoxazole. Where high doses of MTX are given based on large body surface area, urine alkalinization may be indicated.