Trametinib for Refractory Chylous Effusions and Systemic Complications in Children with Noonan Syndrome.
J Pediatr
; 248: 81-88.e1, 2022 09.
Article
em En
| MEDLINE
| ID: mdl-35605646
OBJECTIVE: To evaluate the effect of the RAS-MAPK pathway inhibitor trametinib on medically refractory chylous effusions in 3 hospitalized patients with Noonan syndrome. STUDY DESIGN: Pharmacologic MEK1/2 inhibition has been used to treat conditions associated with Noonan syndrome, given that activation of RAS-MAPK pathway variants leads to downstream MEK activation. We describe our experience with 3 patients with Noonan syndrome (owing to variants in 3 distinct genes) and refractory chylous effusions treated successfully with MEK inhibition. A monitoring protocol was established to standardize medication dosing and monitoring of outcome measures. RESULTS: Subjects demonstrated improvement in lymphatic leak with additional findings of improved growth and normalization of cardiac and hematologic measurements. Trametinib was administered safely, with only moderate skin irritation in 1 subject. CONCLUSIONS: Improvements in a variety of quantifiable measurements highlight the potential utility of MEK1/2 inhibition in patients with Noonan syndrome and life-threatening lymphatic disease. Larger, prospective studies are needed to confirm efficacy and assess long-term safety.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Antineoplásicos
/
Síndrome de Noonan
Tipo de estudo:
Observational_studies
/
Risk_factors_studies
Limite:
Child
/
Humans
Idioma:
En
Revista:
J Pediatr
Ano de publicação:
2022
Tipo de documento:
Article
País de publicação:
Estados Unidos