PMID- 29126203
OWN - NLM
STAT- MEDLINE
DCOM- 20190116
LR  - 20210527
IS  - 1523-5866 (Electronic)
IS  - 1522-8517 (Print)
IS  - 1522-8517 (Linking)
VI  - 20
IP  - 5
DP  - 2018 Apr 9
TI  - A randomized phase II study of everolimus in combination with chemoradiation in 
      newly diagnosed glioblastoma: results of NRG Oncology RTOG 0913.
PG  - 666-673
LID - 10.1093/neuonc/nox209 [doi]
AB  - BACKGROUND: This phase II study was designed to determine the efficacy of the 
      mammalian target of rapamycin (mTOR) inhibitor everolimus administered daily with 
      conventional radiation therapy and chemotherapy in patients with newly diagnosed 
      glioblastoma. METHODS: Patients were randomized to radiation therapy with 
      concurrent and adjuvant temozolomide with or without daily everolimus (10 mg). 
      The primary endpoint was progression-free survival (PFS) and the secondary 
      endpoints were overall survival (OS) and treatment-related toxicities. RESULTS: A 
      total of 171 patients were randomized and deemed eligible for this study. 
      Patients randomized to receive everolimus experienced a significant increase in 
      both grade 4 toxicities, including lymphopenia and thrombocytopenia, and 
      treatment-related deaths. There was no significant difference in PFS between 
      patients randomized to everolimus compared with control (median PFS time: 8.2 vs 
      10.2 mo, respectively; P = 0.79). OS for patients randomized to receive 
      everolimus was inferior to that for control patients (median survival time: 16.5 
      vs 21.2 mo, respectively; P = 0.008). A similar trend was observed in both 
      O6-methylguanine-DNA-methyltransferase promoter hypermethylated and unmethylated 
      tumors. CONCLUSION: Combining everolimus with conventional chemoradiation leads 
      to increased treatment-related toxicities and does not improve PFS in patients 
      with newly diagnosed glioblastoma. Although the median survival time in patients 
      receiving everolimus was comparable to contemporary studies, it was inferior to 
      the control in this randomized study.
FAU - Chinnaiyan, Prakash
AU  - Chinnaiyan P
AD  - William Beaumont Hospital, Royal Oak, Michigan, USA.
FAU - Won, Minhee
AU  - Won M
AD  - NRG Oncology Statistics and Data Management Center, Philadelphia, Pennsylvania, 
      USA.
FAU - Wen, Patrick Y
AU  - Wen PY
AD  - Dana-Farber/Harvard Cancer Center, Boston, Massachusetts, USA.
FAU - Rojiani, Amyn M
AU  - Rojiani AM
AD  - Augusta University-Medical College of Georgia, Augusta, Georgia, USA.
FAU - Werner-Wasik, Maria
AU  - Werner-Wasik M
AD  - Thomas Jefferson University Hospital, Philadelphia, Pennsylvania, USA.
FAU - Shih, Helen A
AU  - Shih HA
AD  - Massachusetts General Hospital, Boston, Massachusetts, USA.
FAU - Ashby, Lynn S
AU  - Ashby LS
AD  - Barrow Neurological Institute accruals under Arizona Oncology Services 
      Foundation, Phoenix, Arizona, USA.
FAU - Michael Yu, Hsiang-Hsuan
AU  - Michael Yu HH
AD  - H. Lee Moffitt Cancer, Tampa, Florida, USA.
FAU - Stieber, Volker W
AU  - Stieber VW
AD  - Novant Health Forsyth Regional Cancer Center accruals under Southeast Cancer 
      Control Consortium, Inc, CCOP, Goldsboro, North Carolina, USA.
FAU - Malone, Shawn C
AU  - Malone SC
AD  - The Ottawa Hospital Regional Cancer Centre, Ottawa, Ontario, Canada.
FAU - Fiveash, John B
AU  - Fiveash JB
AD  - University of Alabama at Birmingham Medical Center, Birmingham, Alabama, USA.
FAU - Mohile, Nimish A
AU  - Mohile NA
AD  - University of Rochester, Rochester, New York, USA.
FAU - Ahluwalia, Manmeet S
AU  - Ahluwalia MS
AD  - Cleveland Clinic Foundation, Cleveland, Ohio, USA.
FAU - Wendland, Merideth M
AU  - Wendland MM
AD  - Willamette Valley Cancer Institute, Eugene, Oregon, USA.
FAU - Stella, Philip J
AU  - Stella PJ
AD  - Saint Joseph Mercy Hospital accruals under Michigan Cancer Research Consortium 
      CCOP, Ypsilanti, Michigan, USA.
FAU - Kee, Andrew Y
AU  - Kee AY
AD  - Legacy Health Systems accruals under Mayo Clinic, Portland, Oregon, USA.
FAU - Mehta, Minesh P
AU  - Mehta MP
AD  - Baptist Hospital of Miami, Miami, Florida, USA.
LA  - eng
GR  - P30 CA013148/CA/NCI NIH HHS/United States
GR  - U10 CA180822/CA/NCI NIH HHS/United States
GR  - U10 CA180868/CA/NCI NIH HHS/United States
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Neuro Oncol
JT  - Neuro-oncology
JID - 100887420
RN  - 7GR28W0FJI (Dacarbazine)
RN  - 9HW64Q8G6G (Everolimus)
RN  - YF1K15M17Y (Temozolomide)
SB  - IM
CIN - Neuro Oncol. 2018 Apr 9;20(5):584-585. PMID: 29608764
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Antineoplastic Combined Chemotherapy Protocols/*therapeutic use
MH  - Brain Neoplasms/pathology/*therapy
MH  - Chemoradiotherapy/*mortality
MH  - Dacarbazine/administration & dosage
MH  - Everolimus/administration & dosage
MH  - Female
MH  - Follow-Up Studies
MH  - Glioblastoma/pathology/*therapy
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Prognosis
MH  - Survival Rate
MH  - Temozolomide/administration & dosage
MH  - Young Adult
PMC - PMC5892159
EDAT- 2017/11/11 06:00
MHDA- 2019/01/17 06:00
PMCR- 2019/04/09
CRDT- 2017/11/11 06:00
PHST- 2017/11/11 06:00 [pubmed]
PHST- 2019/01/17 06:00 [medline]
PHST- 2017/11/11 06:00 [entrez]
PHST- 2019/04/09 00:00 [pmc-release]
AID - 4596531 [pii]
AID - nox209 [pii]
AID - 10.1093/neuonc/nox209 [doi]
PST - ppublish
SO  - Neuro Oncol. 2018 Apr 9;20(5):666-673. doi: 10.1093/neuonc/nox209.