PMID- 26381530
OWN - NLM
STAT- MEDLINE
DCOM- 20160526
LR  - 20210409
IS  - 1531-8249 (Electronic)
IS  - 0364-5134 (Print)
IS  - 0364-5134 (Linking)
VI  - 78
IP  - 6
DP  - 2015 Dec
TI  - Everolimus for subependymal giant cell astrocytoma: 5-year final analysis.
PG  - 929-38
LID - 10.1002/ana.24523 [doi]
AB  - OBJECTIVE: To analyze the cumulative efficacy and safety of everolimus in 
      treating subependymal giant cell astrocytomas (SEGA) associated with tuberous 
      sclerosis complex (TSC) from an open-label phase II study (NCT00411619). Updated 
      data became available from the conclusion of the extension phase and are 
      presented in this >/=5-year analysis. METHODS: Patients aged >/= 3 years with a 
      definite diagnosis of TSC and increasing SEGA lesion size (>/=2 magnetic resonance 
      imaging scans) received everolimus starting at 3mg/m(2) /day (titrated to target 
      blood trough levels of 5-15ng/ml). The primary efficacy endpoint was reduction 
      from baseline in primary SEGA volume. RESULTS: As of the study completion date 
      (January 28, 2014), 22 of 28 (78.6%) initially enrolled patients finished the 
      study per protocol. Median (range) duration of exposure to everolimus was 67.8 
      (4.7-83.2) months; 12 (52.2%) and 14 (60.9%) of 23 patients experienced SEGA 
      volume reductions of >/=50% and >/=30% relative to baseline, respectively, after 60 
      months of treatment. The proportion of patients experiencing daily seizures was 
      reduced from 7 of 26 (26.9%) patients at baseline to 2 of 18 (11.1%) patients at 
      month 60. Most commonly reported adverse events (AEs) were upper respiratory 
      tract infection and stomatitis of mostly grade 1 or 2 severity. No patient 
      discontinued treatment due to AEs. The frequency of emergence of most AEs 
      decreased over the course of the study. INTERPRETATION: Everolimus continues to 
      demonstrate a sustained effect on SEGA tumor reduction over >/=5 years of 
      treatment. Everolimus remained well-tolerated, and no new safety concerns were 
      noted.
CI  - (c) 2015 The Authors. Annals of Neurology published by Wiley Periodicals, Inc. on 
      behalf of American Neurological Association.
FAU - Franz, David N
AU  - Franz DN
AD  - Departments of Pediatrics, Cincinnati Children's Hospital Medical Center, 
      Cincinnati, OH.
AD  - Departments of Neurology, Cincinnati Children's Hospital Medical Center, 
      Cincinnati, OH.
FAU - Agricola, Karen
AU  - Agricola K
AD  - Departments of Pediatrics, Cincinnati Children's Hospital Medical Center, 
      Cincinnati, OH.
AD  - Departments of Neurology, Cincinnati Children's Hospital Medical Center, 
      Cincinnati, OH.
FAU - Mays, Maxwell
AU  - Mays M
AD  - Departments of Pediatrics, Cincinnati Children's Hospital Medical Center, 
      Cincinnati, OH.
AD  - Departments of Neurology, Cincinnati Children's Hospital Medical Center, 
      Cincinnati, OH.
FAU - Tudor, Cindy
AU  - Tudor C
AD  - Departments of Pediatrics, Cincinnati Children's Hospital Medical Center, 
      Cincinnati, OH.
AD  - Departments of Neurology, Cincinnati Children's Hospital Medical Center, 
      Cincinnati, OH.
FAU - Care, Marguerite M
AU  - Care MM
AD  - Departments of Pediatrics, Cincinnati Children's Hospital Medical Center, 
      Cincinnati, OH.
AD  - Departments of Radiology, Cincinnati Children's Hospital Medical Center, 
      Cincinnati, OH.
FAU - Holland-Bouley, Katherine
AU  - Holland-Bouley K
AD  - Departments of Pediatrics, Cincinnati Children's Hospital Medical Center, 
      Cincinnati, OH.
AD  - Departments of Neurology, Cincinnati Children's Hospital Medical Center, 
      Cincinnati, OH.
FAU - Berkowitz, Noah
AU  - Berkowitz N
AD  - Department of Oncology, Novartis Pharmaceuticals Corporation, East Hanover, NJ.
FAU - Miao, Sara
AU  - Miao S
AD  - Department of Oncology, Novartis Pharmaceuticals Corporation, East Hanover, NJ.
FAU - Peyrard, Severine
AU  - Peyrard S
AD  - Department of Oncology, Novartis Pharmaceuticals, Rueil-Malmaison, France.
FAU - Krueger, Darcy A
AU  - Krueger DA
AD  - Departments of Pediatrics, Cincinnati Children's Hospital Medical Center, 
      Cincinnati, OH.
AD  - Departments of Neurology, Cincinnati Children's Hospital Medical Center, 
      Cincinnati, OH.
LA  - eng
SI  - ClinicalTrials.gov/NCT00411619
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20151109
PL  - United States
TA  - Ann Neurol
JT  - Annals of neurology
JID - 7707449
RN  - 0 (Antineoplastic Agents)
RN  - 9HW64Q8G6G (Everolimus)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Antineoplastic Agents/administration & dosage/adverse effects/*pharmacology
MH  - Astrocytoma/*drug therapy/etiology
MH  - Brain Neoplasms/*drug therapy/etiology
MH  - Child
MH  - Child, Preschool
MH  - Everolimus/administration & dosage/adverse effects/*pharmacology
MH  - Female
MH  - Follow-Up Studies
MH  - Humans
MH  - Male
MH  - *Outcome Assessment, Health Care
MH  - Tuberous Sclerosis/*complications
MH  - Young Adult
PMC - PMC5063160
EDAT- 2015/09/19 06:00
MHDA- 2016/05/27 06:00
PMCR- 2016/10/13
CRDT- 2015/09/19 06:00
PHST- 2015/05/08 00:00 [received]
PHST- 2015/09/09 00:00 [revised]
PHST- 2015/09/10 00:00 [accepted]
PHST- 2015/09/19 06:00 [entrez]
PHST- 2015/09/19 06:00 [pubmed]
PHST- 2016/05/27 06:00 [medline]
PHST- 2016/10/13 00:00 [pmc-release]
AID - ANA24523 [pii]
AID - 10.1002/ana.24523 [doi]
PST - ppublish
SO  - Ann Neurol. 2015 Dec;78(6):929-38. doi: 10.1002/ana.24523. Epub 2015 Nov 9.