دورية أكاديمية
A pooled subgroup analysis of glucarpidase treatment in 86 pediatric, adolescent, and young adult patients receiving high-dose methotrexate therapy in open-label trials
| العنوان: | A pooled subgroup analysis of glucarpidase treatment in 86 pediatric, adolescent, and young adult patients receiving high-dose methotrexate therapy in open-label trials |
|---|---|
| المؤلفون: | Janeway, Katherine, Schwartz, Stefan, Daugherty, Claire, Gallardo, Eva, Hill, Christon, Gros Subías, Luis |
| المساهمون: | Institut Català de la Salut, Janeway KA Dana-Farber/Boston Children’s Cancer and Blood Disorders Center and Harvard Medical School, Boston, Massachusetts, USA. Gros L Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Servei d'Hematologia i Oncologia Pediàtriques, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Schwartz S Department of Hematology, Oncology and Tumor Immunology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität and Humboldt-Universität zu Berlin, Campus Benjamin Franklin, Berlin, Germany. Daugherty C, Hill C BTG International Inc., Conshohocken, Pennsylvania, USA. Gallardo E Protherics Medicines Development Ltd., London, UK, Vall d'Hebron Barcelona Hospital Campus |
| المصدر: | Scientia |
| بيانات النشر: | Wiley |
| سنة النشر: | 2023 |
| مصطلحات موضوعية: | Infants, Sang - Malalties - Tractament, Àcid fòlic, CHEMICALS AND DRUGS::Chemical Actions and Uses::Pharmacologic Actions::Molecular Mechanisms of Pharmacological Action::Enzyme Inhibitors::Folic Acid Antagonists, Other subheadings::Other subheadings::/therapeutic use, DISEASES::Neoplasms::Neoplasms by Site::Hematologic Neoplasms, NAMED GROUPS::Persons::Age Groups::Child, COMPUESTOS QUÍMICOS Y DROGAS::acciones y usos químicos::acciones farmacológicas::mecanismos moleculares de acción farmacológica::inhibidores enzimáticos::antagonistas del ácido fólico, Otros calificadores::Otros calificadores::/uso terapéutico, ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias hematológicas, DENOMINACIONES DE GRUPOS::personas::Grupos de Edad::niño |
| الوصف: | Acute kidney injury; Glucarpidase; Methotrexate ; Lesió renal aguda; Glucarpidasa; Metotrexat ; Lesión renal aguda; Glucarpidasa; Metotrexato ; Background Delayed methotrexate elimination can occur in patients undergoing high-dose methotrexate cancer treatment. Effectiveness of glucarpidase for rapidly reducing methotrexate concentrations was shown in compassionate-use trials in patients aged 0–84 years. Methods We performed post hoc analyses of infants (≥28 days to <2 years), children (≥2 to <12 years), adolescents (≥12 to <15 years), and young adults (≥15 to <25 years) from four multicenter, open-label, single-arm, glucarpidase compassionate-use trials. Patients had toxic methotrexate levels due to delayed methotrexate elimination and/or renal dysfunction, and received glucarpidase (50 U/kg). The primary endpoint was clinically important reduction (CIR) in plasma methotrexate (methotrexate ≤1 μmol/L at all post-glucarpidase measurements) based on high-performance liquid chromatography. Results Among 86 patients included in efficacy analyses, CIR was achieved by zero of one infant (0.0%), five of 16 children (31.3%), seven of 24 adolescents (29.2%), and 26/45 young adults (57.8%). Median methotrexate reduction was 98.7% or higher in each group 15 minutes post-glucarpidase. Patients with pre-glucarpidase methotrexate less than 50 μmol/L (35/42, 83.3%) were more likely to achieve CIR than those with methotrexate 50 μmol/L or higher (1/37, 2.7%). The most common treatment-related adverse event was paresthesia, occurring in three adolescents (4.5%) and six young adults (5.2%). No other treatment-related adverse event occurred in 5% or higher of any age group. Conclusion After accounting for pre-glucarpidase methotrexate levels, glucarpidase efficacy at inducing CIR in pediatric/young adult patients was consistent, with efficacy observed in the overall study population (i.e., patients aged 0–84), and no unexpected safety findings were observed. These findings demonstrate glucarpidase (50 U/kg) is an ... |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1545-5017 |
| العلاقة: | Pediatric Blood & Cancer;70(9); https://doi.org/10.1002/pbc.30506Test; Janeway KA, Gros L, Schwartz S, Daugherty C, Gallardo E, Hill C, et al. A pooled subgroup analysis of glucarpidase treatment in 86 pediatric, adolescent, and young adult patients receiving high-dose methotrexate therapy in open-label trials. Pediatr Blood Cancer. 2023 Sep;70(9):e30506.; https://hdl.handle.net/11351/10260Test; 001017514700001 |
| DOI: | 10.1002/pbc.30506 |
| الإتاحة: | https://doi.org/10.1002/pbc.30506Test https://hdl.handle.net/11351/10260Test |
| حقوق: | Attribution-NonCommercial-NoDerivatives 4.0 International ; http://creativecommons.org/licenses/by-nc-nd/4.0Test/ ; info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.D80EA4B1 |
| قاعدة البيانات: | BASE |
| تدمد: | 15455017 |
|---|---|
| DOI: | 10.1002/pbc.30506 |