Dexamethasone increases hepatotoxicity of MTX in children with brain tumors.
BACKGROUND
In the treatment of children with brain tumors, dexamethasone and methotrexate are often utilized simultaneously. As previously shown, dexamethasone can reduce the efficacy of methotrexate in vitro (Anticancer Res. 14: 1585-8). Consequently, DEX has been avoided during high dose methotrexate infusions in a pilot study.


METHODS
Side effects of methotrexate with dexamethasone (N = 33) were retrospectively compared with the side effects of methotrexate without dexamethasone (N = 24).


RESULTS
No serious brain edema in any of the groups was observed; there was no difference in bone marrow toxicity, or mucositis. Liver enzymes, however, were significantly higher when methotrexate was given with dexamethasone: GOT [glutamate oxalacetate transaminase] 76 +/- 73 versus 19 +/- 12, GPT (glutamate pyrovate transaminase) 140 +/- 199 versus 39 +/- 31 IU/I (P < 0.01). This higher hepatotoxicity was not related to differences in methotrexate serum-levels.


CONCLUSIONS
Dexamethasone can be eliminated from high dose methotrexate protocols for children.
Department of Pediatric Oncology, Alberta Children's Hospital, Calgary, Canada. johannes.wolff@crha-health.ab.ca
J E
JE
Wolff
H
H
Hauch
J
J
Kühl
R M
RM
Egeler
H
H
Jürgens
D000293:Adolescent; D000410:Alanine Transaminase / Q000378:metabolism; D001219:Aspartate Aminotransferases / Q000378:metabolism; D001932:Brain Neoplasms / Q000188:drug therapy*; D002648:Child; D002675:Child, Preschool; D003907:Dexamethasone / Q000008:administration & dosage / Q000009:adverse effects*; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007223:Infant; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects*; D012189:Retrospective Studies
D003907:Dexamethasone; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D008727:Methotrexate