Klin Onkol 2002; 15(6): 230-233.
Summary:
Background: Methotrexate is one of the most frequently used cytotoxic drugs in pediatric oncology. Its dosing range used in the clinic is unusually broad comparing with other cornrnonly used anticancer drugs. Despite the longterm use of methotrexate in treatment of selected malignancies, its clinical use is still covered with a lot of empirics and its dosage and metabolism poorly substantiated by relevant subject-oriented data.
Type of study and cohort: Current knowledge on methotrexate metabolism was reviewed and potential of efficacy and toxicity prediction outlined. A case report of unexpected and clinically serious CNS toxicity that followed adrninistration ofhigh-dose methotrexate is presented. Methods ani results: A nine year old boy is treated for acute hybrid bcr-abl positive leukemia using using the protocol ALL-BFM95 containing a block of 5 g.m-2 high-dose methotrexate. On the fourth day of the flfst block an episode of severe neurotoxicity occurred with convulsions and deep coma (Glasgow grade 5) requiring emergent resuscitation care with artificial ventilation for a period of 30 hours. We observed a markedly prolonged decrease of plasma methotrexate levels.
Conclusions: Unexpected and sometimes life-threatening toxicity is a complication of treatment of even those anticancer drugs with proven efficacy record. For such drugs as of yet indispensable in clinical oncology, it is important to concentrate effort to devise methods capable of predicting potential and possibly fata! therapy-related side effect.
