A phase II trial of selumetinib in children with recurrent optic pathway and hypothalamic low-grade glioma without NF1: a Pediatric Brain Tumor Consortium study.

Autor:	Fangusaro J; Department of Hematology, Oncology, and Stem Cell Transplantation, Children's Healthcare of Atlanta and Emory University, Atlanta, Georgia, USA., Onar-Thomas A; Department of Biostatistics St. Jude Children's Research Center, Memphis, Tennessee, USA., Poussaint TY; St. Jude Children's Research Center, Memphis, Tennessee, USA.; Department of Radiology, Boston Children's Hospital, Boston, Massachusetts, USA., Wu S; Department of Biostatistics St. Jude Children's Research Center, Memphis, Tennessee, USA., Ligon AH; Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA., Lindeman N; Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA., Campagne O; Department of Pharmaceutical Sciences St. Jude Children's Research Center, Memphis, Tennessee, USA., Banerjee A; Center for Cancer and Blood Disorders, University of California, San Francisco, California, USA., Gururangan S; Department of Neurosurgery, University of Florida, Gainesville, Florida, USA., Kilburn LB; Division of Oncology Children's National Hospital , Washington DC, USA., Goldman S; Children's National Hospital, Washington DC, USA.; Department of Hematology, Oncology, Neuro-Oncology and Stem Cell Transplantation., Qaddoumi I; Department of Oncology St. Jude Children's Research Center, Memphis, Tennessee, USA., Baxter P; Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois, USA.; Department of Hematology and Oncology, Texas Children's Hospital, Houston, Texas, USA., Vezina G; Department of Radiology Children's National Hospital , Washington DC, USA., Bregman C; Department of Medical Imaging., Patay Z; Department of Diagnostic Imaging St. Jude Children's Research Center, Memphis, Tennessee, USA., Jones JY; Department of Radiology Nationwide Children's Hospital, Columbus, Ohio, USA., Stewart CF; Department of Pharmaceutical Sciences St. Jude Children's Research Center, Memphis, Tennessee, USA., Fisher MJ; Nationwide Children's Hospital, Columbus, Ohio, USA.; Division of Oncology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA., Doyle LA; Investigational Drug Branch, National Cancer Institute and Cancer Therapy Evaluation Program, Rockville, Maryland, USA., Smith M; Clinical Investigation Branch, National Cancer Institute and Cancer Therapy Evaluation Program, Rockville, Maryland, USA., Dunkel IJ; National Cancer Institute and Cancer Therapy Evaluation Program, Rockville, Maryland, USA.; Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, New York, USA., Fouladi M; Department of Hematology and Oncology Nationwide Children's Hospital, Columbus, Ohio, USA.
Jazyk:	angličtina
Zdroj:	Neuro-oncology [Neuro Oncol] 2021 Oct 01; Vol. 23 (10), pp. 1777-1788.
DOI:	10.1093/neuonc/noab047
Abstrakt:	Background: Pediatric low-grade gliomas (pLGGs) are the most common childhood brain tumor. Progression-free survival (PFS) is much lower than overall survival, emphasizing the need for alternative treatments. Sporadic (without neurofibromatosis type 1) optic pathway and hypothalamic gliomas (OPHGs) are often multiply recurrent and cause significant visual deficits. Recently, there has been a prioritization of functional outcomes. Methods: We present results from children with recurrent/progressive OPHGs treated on a PBTC (Pediatric Brain Tumor Consortium) phase II trial evaluating efficacy of selumetinib (AZD6244, ARRY-142886) a MEK-1/2 inhibitor. Stratum 4 of PBTC-029 included patients with sporadic recurrent/progressive OPHGs treated with selumetinib at the recommended phase II dose (25mg/m2/dose BID) for a maximum of 26 courses. Results: Twenty-five eligible and evaluable patients were enrolled with a median of 4 (1-11) previous therapies. Six of 25 (24%) had partial response, 14/25 (56%) had stable disease, and 5 (20%) had progressive disease while on treatment. The median treatment courses were 26 (2-26); 14/25 patients completed all 26 courses. Two-year PFS was 78 ± 8.5%. Nineteen of 25 patients were evaluable for visual acuity which improved in 4/19 patients (21%), was stable in 13/19 (68%), and worsened in 2/19 (11%). Five of 19 patients (26%) had improved visual fields and 14/19 (74%) were stable. The most common toxicities were grade 1/2 CPK elevation, anemia, diarrhea, headache, nausea/emesis, fatigue, AST and ALT increase, hypoalbuminemia, and rash. Conclusions: Selumetinib was tolerable and led to responses and prolonged disease stability in children with recurrent/progressive OPHGs based upon radiographic response, PFS, and visual outcomes. (© The Author(s) 2021. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu