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Evaluation of serious adverse events in patients treated with protocols including methotrexate infusions
Abstract:
During the period 1979 to 1992 we treated 141 children for various malignant 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 continuously during the infusions. In this study, we evaluated the occurrence of serious untoward reactions to MTX infusions. Impaired renal function with delayed drug elimination was seen in seven patients, all boys, especially after short infusion times. All recovered completely without any serious clinical symptoms. In three leukemia patients who later died from resistant disease, we observed late neurological disturbances and computer tomography (CT) brain scan abnormalities. Pharmacokinetic data from the patients with complications are described and confirm that serial MTX concentration monitoring is the most important early indicator of renal toxicity.
Insights
High-dose methotrexate (MTX) infusions are safe for pediatric cancer patients, with no fatal complications observed. Monitoring MTX levels is crucial for early detection of kidney issues and potential neurological side effects.
Area of Science:
- Pediatric Oncology
- Clinical Pharmacology
Background:
- Methotrexate (MTX) is a critical chemotherapeutic agent used in treating various pediatric malignancies.
- High-dose MTX protocols require careful monitoring due to potential toxicities.
Purpose of the Study:
- To evaluate the safety and adverse reactions of high-dose methotrexate (MTX) infusions in children with malignant diseases.
- To identify early indicators of MTX-related toxicity.
Main Methods:
- Retrospective analysis of 141 children treated with MTX infusions (0.5–33.6 g/m2) between 1979 and 1992.
- Continuous monitoring of serum MTX concentrations and pharmacokinetic data during infusions.
- Evaluation of adverse events, including renal function and neurological disturbances.
Main Results:
- No fatal complications occurred during 922 MTX courses.
- Seven patients (all boys) experienced impaired renal function with delayed MTX elimination, particularly after short infusions; all recovered fully.
- Late neurological disturbances and brain CT abnormalities were observed in three leukemia patients who succumbed to resistant disease.
Conclusions:
- High-dose MTX infusions are generally well-tolerated in pediatric cancer patients.
- Serial MTX concentration monitoring is essential for early detection of renal toxicity.
- Potential for delayed MTX elimination and neurological complications necessitates vigilant patient observation.