Document Detail


The inability of oral leucovorin to elevate CSF 5-methyl-tetrahydrofolate following high dose intravenous methotrexate therapy.
MedLine Citation:
PMID:  6611387     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Osteosarcoma patients free of CNS metastases are at risk for acquiring leukoencephalopathy after receiving multiple courses of high dose intravenous methotrexate followed by oral leucovorin rescue (MTX-LV). A prospective study of the adequacy of CNS rescue of MTX biochemical toxicity by oral leucovorin was undertaken in newly diagnosed neurologically normal osteosarcoma patients. Prior to surgical resection of the primary tumor, ten patients received 4 weekly courses of MTX-LV. During the fourth weekly MTX-LV treatment, 0 and 72 hr serum and CSF determinations of MTX, 5-methyl-tetrahydrofolate (5-MTHF) and LV were made. No CSF MTX was detectable at 0 hr in any patient, but a significant elevation in CSF MTX occurred in 9/9 patients at 72 hr (mean 47.2 +/- 31.8 ng/ml or 1.04 +/- 0.7 X 10(-7) M). There was no significant change in mean CSF 5-MTHF over 72 hr despite a rise in serum 5-MTHF. MTX exceeded 5-MTHF in 6/9 patients in CSF, whereas only 3/8 patients had higher MTX in the serum at 72 hr. No acute systemic or neurotoxicity was seen. The failure of oral leucovorin to consistently elevate CSF 5-MTHF levels at 72 hr in the context of significant levels of CSF MTX may result in intermittent CNS folate deficiency. The clinical and pathological syndrome of leukoencephalopathy may be related to this phenomenon and may evolve after repeated MTX-LV treatments.
Authors:
J Allen; G Rosen; H Juergens; B Mehta
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of neuro-oncology     Volume:  1     ISSN:  0167-594X     ISO Abbreviation:  J. Neurooncol.     Publication Date:  1983  
Date Detail:
Created Date:  1984-09-19     Completed Date:  1984-09-19     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8309335     Medline TA:  J Neurooncol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  39-44     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Adult
Child
Drug Therapy, Combination
Female
Humans
Leucovorin / therapeutic use*
Male
Methotrexate / administration & dosage*,  adverse effects
Osteosarcoma / blood,  cerebrospinal fluid,  drug therapy*
Tetrahydrofolates / blood,  cerebrospinal fluid*
Chemical
Reg. No./Substance:
0/Tetrahydrofolates; 134-35-0/5-methyltetrahydrofolate; 58-05-9/Leucovorin; 59-05-2/Methotrexate

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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