A phase I/II study of ribociclib following radiation therapy in children with newly diagnosed diffuse intrinsic pontine glioma (DIPG).
Adolescent
Adult
Aminopyridines
/ pharmacokinetics
Brain Stem Neoplasms
/ pathology
Chemoradiotherapy
/ methods
Child
Child, Preschool
Diffuse Intrinsic Pontine Glioma
/ pathology
Female
Follow-Up Studies
Humans
Male
Maximum Tolerated Dose
Prognosis
Purines
/ pharmacokinetics
Tissue Distribution
Young Adult
Pediatric diffuse intrinsic pontine glioma (DIPG)
Pediatric diffuse midline glioma (DMG)
Ribociclib
Journal
Journal of neuro-oncology
ISSN: 1573-7373
Titre abrégé: J Neurooncol
Pays: United States
ID NLM: 8309335
Informations de publication
Date de publication:
Sep 2020
Sep 2020
Historique:
received:
04
08
2020
accepted:
01
10
2020
pubmed:
10
10
2020
medline:
20
8
2021
entrez:
9
10
2020
Statut:
ppublish
Résumé
Cyclin-dependent kinase-retinoblastoma (CDK-RB) pathway is dysregulated in some diffuse intrinsic pontine gliomas (DIPG). We evaluated safety, feasibility, and early efficacy of the CDK4/6-inhibitor ribociclib, administered following radiotherapy in newly-diagnosed DIPG patients. Following radiotherapy, eligible patients received ribociclib in 28-day cycles (350 mg/m The study included 10 evaluable patients, 9 DIPG and 1 diffuse midline glioma (DMG)-all 3.7 to 19.8 years of age. The median number of courses was 8 (range 3-14). Three patients required dose reduction for grade-4 neutropenia, and 1 discontinued therapy for hematological toxicity following course 4. The most common grade-3/4 toxicity was myelosuppression. After 2 courses, MRI evaluations in 4 patients revealed increased necrotic volume, associated with new neurological symptoms in 3 patients. The 1-year and median OS for DIPG was 89% and 16.1 months (range 10-30), respectively; the DMG patient died at 6 months post-diagnosis. Five patients donated brain tissue and tumor; 3 were RB+ . Ribociclib administered following radiotherapy is feasible in DIPG and DMG. Increased tumor necrosis may represent a treatment effect. These data warrant further prospective volumetric analyses of tumors with necrosis. Feasibility and stabilization findings support further investigation of ribociclib in combination therapies. NCT02607124.
Identifiants
pubmed: 33034839
doi: 10.1007/s11060-020-03641-2
pii: 10.1007/s11060-020-03641-2
doi:
Substances chimiques
Aminopyridines
0
Purines
0
ribociclib
TK8ERE8P56
Banques de données
ClinicalTrials.gov
['NCT02607124']
Types de publication
Clinical Trial, Phase I
Clinical Trial, Phase II
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
511-522Références
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