Dose-individualization Efficiently Maintains Sufficient Exposure to Methotrexate without Additional Toxicity in High-dose Methotrexate Regimens for Pediatric Acute Lymphoblastic Leukemia.
Curr Med Sci
; 42(4): 769-777, 2022 Aug.
Article
em En
| MEDLINE
| ID: mdl-35864414
ABSTRACT
OBJECTIVE:
Methotrexate (MTX) can be safely administered to most patients but may cause severe toxicity in others. This study aimed to summarize the characteristics of high-dose methotrexate (HD-MTX) chemotherapy and to evaluate whether the modified dose-adjustment program was able to improve the maintenance of sufficient MTX exposure levels while minimizing toxicities.METHODS:
We evaluated 1172 cycles of high-dose MTX chemotherapy from 294 patients who were treated according to the CCCG-ALL-2015 protocol (clinical trial number ChiCTR-IPR-14005706) and analyzed the data of actual MTX dosage, MTX concentration, toxicity, and prognosis. We compared data between the dose-adjustment Program 1 (fixed 20% reduction in dose) and the dose-adjustment Program 2 (dose-individualization based on reassessment of the creatine clearance rate and the MTX concentration-monitoring point at 16 h), which were applied if the MTX clearance was delayed in the previous cycle.RESULTS:
The patients who used Program 2 had higher actual MTX infusion doses and infusion rates and were able to better maintain the MTX concentration at 44 h at the established target value than those on Program 1 (P<0.001). No significant differences in toxicities were found between these two programs except that abnormal serum potassium levels and prolonged myelosuppression in intermediate-risk/high-risk patients were more frequently observed in patients using Program 2 (P<0.001). No significant correlations were observed between the MTX dose, dose-adjustment programs, or MTX concentrations and relapse-free survival.CONCLUSION:
Adjusting the MTX dose using Program 2 is more efficient for maintaining sufficient MTX exposure without significantly increasing the toxicity.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Metotrexato
/
Leucemia-Linfoma Linfoblástico de Células Precursoras
Tipo de estudo:
Guideline
/
Prognostic_studies
Limite:
Child
/
Humans
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article