PMID- 27844311
OWN - NLM
STAT- MEDLINE
DCOM- 20171226
LR  - 20191210
IS  - 1573-7373 (Electronic)
IS  - 0167-594X (Linking)
VI  - 131
IP  - 1
DP  - 2017 Jan
TI  - Phase II study of MEDI-575, an anti-platelet-derived growth factor-alpha antibody, in 
      patients with recurrent glioblastoma.
PG  - 185-191
LID - 10.1007/s11060-016-2287-6 [doi]
AB  - MEDI-575, an immunoglobulin G2kappa monoclonal antibody, selectively binds to 
      platelet-derived growth factor-alpha receptor (PDGFR-alpha) with high specificity. This 
      multicenter, single-arm, open-label, phase II study evaluated the efficacy and 
      safety of MEDI-575 in patients with recurrent glioblastoma. Adults with first 
      recurrence of glioblastoma following surgery, temozolomide, and radiation 
      received MEDI-575 25 mg/kg intravenously over 60 min every 21 days until disease 
      progression or unacceptable toxicity. Six-month progression-free survival rate 
      (PFS-6) was the primary end point; secondary measures included response rate, 
      overall survival (OS), and safety/tolerability. PDGFR-alpha expression was evaluated 
      by immunohistochemistry. Fifty-six patients were enrolled; median age was 56.5 
      years (range 23-79), 66 % were male, and 66 % were aged >/=65 years. PFS-6 was 
      15.4 % [90 % confidence interval (CI) 8.1-24.9]. No complete or partial responses 
      were observed; 23 (41.1 %) patients had stable disease as best response. Median 
      PFS was 1.4 months (90 % CI 1.4, 1.8); median OS was 9.7 months (90 % CI 6.5, 
      11.8). The most common treatment-related adverse events (AEs) were diarrhea 
      (16 %), nausea (13 %), and fatigue (13 %). Twelve (21 %) patients reported grade 
      >/=3 AEs, with hydrocephalus (n = 3), dysphagia (n = 2), and convulsion (n = 2) 
      reported in more than 1 patient. Two patients had treatment-related Grade >/=3 AEs 
      of decreased lymphocyte count and asthenia (n = 1 each). Seven patients (13 %) 
      discontinued MEDI-575 owing to AEs. Labeling of PDGFRalpha in glioblastoma cells and 
      tumor-associated stromal cells was highly variable, with no correlation with PFS. 
      MEDI-575, although well tolerated, had limited clinical activity in recurrent 
      glioblastoma.
FAU - Phuphanich, Surasak
AU  - Phuphanich S
AD  - Johnnie L. Cochran Jr. Brain Tumor Center, Cedars-Sinai Medical Center, 127 South 
      San Vicente Blvd, Los Angeles, CA, USA. phuphanich@hotmail.com.
AD  - Department of Neurology, Division of Neuro-Oncology, Barrow Neurological 
      Institute, 240 West Thomas Road, Suite 400, Phoenix, AZ, 85013, USA. 
      phuphanich@hotmail.com.
FAU - Raizer, Jeffrey
AU  - Raizer J
AD  - Northwestern Brain Tumor Institute, Northwestern University, 675 N. St. Clair, 
      Chicago, IL, 60611, USA.
FAU - Chamberlain, Marc
AU  - Chamberlain M
AD  - University of Washington, 1959 NE Pacific St., 8th Floor, Seattle, WA, 98195, 
      USA.
FAU - Canelos, Paola
AU  - Canelos P
AD  - MedImmune, 1 MedImmune Way, Gaithersburg, MD, 20878, USA.
FAU - Narwal, Rajesh
AU  - Narwal R
AD  - MedImmune, 1 MedImmune Way, Gaithersburg, MD, 20878, USA.
FAU - Hong, Shengyan
AU  - Hong S
AD  - MedImmune, 1 MedImmune Way, Gaithersburg, MD, 20878, USA.
FAU - Miday, Robert
AU  - Miday R
AD  - MedImmune, 1 MedImmune Way, Gaithersburg, MD, 20878, USA.
FAU - Nade, Minal
AU  - Nade M
AD  - MedImmune, 1 MedImmune Way, Gaithersburg, MD, 20878, USA.
FAU - Laubscher, Kevin
AU  - Laubscher K
AD  - MedImmune, 1 MedImmune Way, Gaithersburg, MD, 20878, USA.
LA  - eng
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
DEP - 20161114
PL  - United States
TA  - J Neurooncol
JT  - Journal of neuro-oncology
JID - 8309335
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Antineoplastic Agents, Immunological)
RN  - 2XY62K75UV (Tovetumab)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Antibodies, Monoclonal, Humanized/*therapeutic use
MH  - Antineoplastic Agents, Immunological/*therapeutic use
MH  - Brain Neoplasms/diagnostic imaging/*drug therapy/mortality
MH  - Disease-Free Survival
MH  - Female
MH  - Glioblastoma/diagnostic imaging/*drug therapy/mortality
MH  - Humans
MH  - Magnetic Resonance Imaging
MH  - Male
MH  - Middle Aged
MH  - Neoplasm Recurrence, Local/drug therapy/mortality
MH  - Treatment Outcome
MH  - United States
MH  - Young Adult
OTO - NOTNLM
OT  - Anti-PDGFR-alpha
OT  - Monoclonal antibody
OT  - Progression-free survival
OT  - Safety
OT  - Treatment outcomes
EDAT- 2016/11/16 06:00
MHDA- 2017/12/27 06:00
CRDT- 2016/11/16 06:00
PHST- 2016/06/15 00:00 [received]
PHST- 2016/10/09 00:00 [accepted]
PHST- 2016/11/16 06:00 [pubmed]
PHST- 2017/12/27 06:00 [medline]
PHST- 2016/11/16 06:00 [entrez]
AID - 10.1007/s11060-016-2287-6 [pii]
AID - 10.1007/s11060-016-2287-6 [doi]
PST - ppublish
SO  - J Neurooncol. 2017 Jan;131(1):185-191. doi: 10.1007/s11060-016-2287-6. Epub 2016 
      Nov 14.