PMID- 26858193
OWN - NLM
STAT- MEDLINE
DCOM- 20170509
LR  - 20171228
IS  - 1097-6833 (Electronic)
IS  - 0022-3476 (Linking)
VI  - 172
DP  - 2016 May
TI  - Safety of Everolimus in Patients Younger than 3 Years of Age: Results from 
      EXIST-1, a Randomized, Controlled Clinical Trial.
PG  - 151-155.e1
LID - S0022-3476(16)00029-9 [pii]
LID - 10.1016/j.jpeds.2016.01.027 [doi]
AB  - OBJECTIVES: To assess the long-term safety of everolimus in young children with 
      tuberous sclerosis complex (TSC)-associated subependymal giant cell astrocytoma 
      (SEGA). STUDY DESIGN: EXamining everolimus In a Study of Tuberous Sclerosis 
      Complex-1 (EXIST-1) was a multicenter, randomized, double-blind phase 3 study 
      with an open-label extension evaluating the efficacy and tolerability of 
      everolimus in patients with TSC-associated SEGA. Everolimus was initiated at 
      4.5 mg/m(2)/day and titrated to blood trough levels of 5-15 ng/mL. Post hoc 
      analysis of safety data (adverse events [AEs]) was performed in a subgroup of 
      patients aged <3 years at everolimus initiation. RESULTS: Eighteen patients 
      (median age 1.82 years) were included; 16 were still receiving everolimus at the 
      analysis cut-off date of January 11, 2013. Median everolimus exposure was 
      31.1 months (range, 11.5-39 months). One patient discontinued treatment because 
      of AEs (ie, Acinetobacter bacteremia, increased blood alkaline phosphatase, and 
      viral infection). AEs were reported in all patients, but events were mostly grade 
      1/2 in severity; 12 patients (66.7%) experienced grade 3 events, and 2 patients 
      (11.1%) reported grade 4 events. The most common AEs were stomatitis, cough, 
      pharyngitis, and pyrexia; no new safety issues were identified in this 
      population. Serious AEs were reported in 50% of patients; these were suspected to 
      be medication related in 4 patients (22.2%). CONCLUSIONS: Everolimus appears to 
      be a safe therapeutic option for patients aged <3 years with TSC-associated SEGA. 
      The small sample size in this subpopulation limits interpretation of the results; 
      additional studies in the pediatric population are needed and are underway. TRIAL 
      REGISTRATION: ClinicalTrials.gov: NCT00789828.
CI  - Copyright (c) 2016 Elsevier Inc. All rights reserved.
FAU - Jozwiak, Sergiusz
AU  - Jozwiak S
AD  - Department of Pediatric Neurology, Warsaw Medical University, Warsaw, Poland; 
      Department of Neurology and Epileptology, The Children's Memorial Health 
      Institute, Warsaw, Poland. Electronic address: sergiusz.jozwiak@wum.edu.pl.
FAU - Kotulska, Katarzyna
AU  - Kotulska K
AD  - Department of Neurology and Epileptology, The Children's Memorial Health 
      Institute, Warsaw, Poland.
FAU - Berkowitz, Noah
AU  - Berkowitz N
AD  - Department of Oncology, Novartis Pharmaceuticals Corporation, Florham Park, NJ.
FAU - Brechenmacher, Thomas
AU  - Brechenmacher T
AD  - Department of Oncology, Novartis Pharmaceuticals S.A.S., Rueil-Malmaison, France.
FAU - Franz, David Neal
AU  - Franz DN
AD  - Department of Neurology, Cincinnati Children's Hospital Medical Center, 
      Cincinnati, OH.
LA  - eng
SI  - ClinicalTrials.gov/NCT00789828
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20160206
PL  - United States
TA  - J Pediatr
JT  - The Journal of pediatrics
JID - 0375410
RN  - 0 (Immunosuppressive Agents)
RN  - 9HW64Q8G6G (Everolimus)
SB  - IM
MH  - Astrocytoma/complications/*drug therapy
MH  - Child, Preschool
MH  - Everolimus/adverse effects/*therapeutic use
MH  - Female
MH  - Humans
MH  - Immunosuppressive Agents/adverse effects/*therapeutic use
MH  - Infant
MH  - Male
MH  - No-Observed-Adverse-Effect Level
MH  - Treatment Outcome
MH  - Tuberous Sclerosis/complications/*drug therapy
EDAT- 2016/02/10 06:00
MHDA- 2017/05/10 06:00
CRDT- 2016/02/10 06:00
PHST- 2015/08/17 00:00 [received]
PHST- 2015/11/13 00:00 [revised]
PHST- 2016/01/08 00:00 [accepted]
PHST- 2016/02/10 06:00 [entrez]
PHST- 2016/02/10 06:00 [pubmed]
PHST- 2017/05/10 06:00 [medline]
AID - S0022-3476(16)00029-9 [pii]
AID - 10.1016/j.jpeds.2016.01.027 [doi]
PST - ppublish
SO  - J Pediatr. 2016 May;172:151-155.e1. doi: 10.1016/j.jpeds.2016.01.027. Epub 2016 
      Feb 6.