Risk factors for high-dose methotrexate associated toxicities in patients with primary central nervous system lymphoma.
J Clin Pharm Ther
; 47(12): 2196-2204, 2022 Dec.
Article
en En
| MEDLINE
| ID: mdl-36259502
ABSTRACT
WHAT IS KNOWN AND OBJECTIVE:
Methotrexate (MTX) is an antimetabolic antitumor drug with high individual differences and may lead to severe toxicities in a considerable number of patients. This study aimed to explore the factors influencing major adverse events in patients with primary central nervous system lymphoma treated with high-dose MTX (HD-MTX), which could be useful in clinical practice.METHODS:
Fifty-four patients who received 175 courses of MTX at 3-8 g/m2 between January 2015 and December 2016 were enrolled in this study. We assessed the association between clinical characteristics, MTX pharmacokinetics, MTX delayed elimination, and adverse events, including hepatotoxicity, acute kidney injury (AKI), and myelosuppression. RESULTS ANDDISCUSSION:
A total of 124 adverse events occurred after MTX infusion. Using independent sample t-tests, we found that patients with myelosuppression had higher MTX area under the concentration-time curve up to 48 h after infusion (AUC0-48h ) (p = 0.001) and MTX peak concentration (Cmax ) (p = 0.002). MTX concentrations at 48 and 72 h were higher in patients with AKI than in those without (p = 0.034 and p = 0.041, respectively). Using chi-square tests, we found that AKI was correlated with MTX elimination at either 48 h or 72 h (22.1% vs. 8.2%, p = 0.010). By multivariate logistic regression model, our results showed that baseline level of ALT and WBC had a significant effect on hepatotoxicity (OR = 1.079, 95% CI 1.044-1.116, p = 6.9 × 10-6 ; OR = 0.808, 95% CI 0.711-0.917, p = 0.001, respectively). Patient's age, eGFR before MTX infusion, and co-administration of vindesine had a significant effect on AKI (OR = 0.960, 95% CI 0.935-0.986, p = 0.003; OR = 1.009, 95% CI 1.001-1.017, p = 0.034; OR = 5.463, 95% CI 1.793-16.646, p = 0.003, respectively). LDH and Co-administration of vindesine had a significant effect on myelosuppression (OR = 0.985, 95% CI 0.972-0.998, p = 0.025; OR = 3.070, 95% CI 1.032-9.133, p = 0.044). WHAT IS NEW ANDCONCLUSION:
Our study demonstrated that co-administration of VDS, eGFR before MTX infusion, and the baseline index of laboratory examinations including ALT, WBC, LDH may be useful biomarkers for predicting MTX-induced toxicities.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos
/
Enfermedad Hepática Inducida por Sustancias y Drogas
/
Lesión Renal Aguda
/
Linfoma
Tipo de estudio:
Etiology_studies
/
Prognostic_studies
/
Risk_factors_studies
Límite:
Humans
Idioma:
En
Revista:
J Clin Pharm Ther
Asunto de la revista:
FARMACIA
/
TERAPEUTICA
Año:
2022
Tipo del documento:
Article
País de afiliación:
China