EVALUATION OF SERIOUS ADVERSE EVENTS IN PATIENTS TREATED WITH PROTOCOLS INCLUDING METHOTREXATE INFUSIONS

During the period 1979 to 1999 we treated 141 children for various mal ignant diseases with protocols including methotrexate (MTX) infusions in doses ranging from 0.5 to 33.6 g/m2 During a total of 922 courses, there were no fatal complications associated with MTX treatment. Serum MTX concentration and pharmacokinetic data were monitored continuousl y during the infusions. In this study, we evaluated the occurrence of serious untoward reactions to MTX infusions. Impaired renal function w ith delayed drug elimination was seen in seven patients, all boys, esp ecially after short infusion times. All recovered completely without a ny serious clinical symptoms. In three leukemia patients who later die d from resistant disease, we observed late neurological disturbances a nd computer tomography (CT) brain scan abnormalities. Pharmacokinetic data from the patients with complications are described and confirm th at serial MTX concentration monitoring is the most important early ind icator of renal toxicity.