PMID- 32642720
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220415
IS  - 2632-2498 (Electronic)
IS  - 2632-2498 (Linking)
VI  - 2
IP  - 1
DP  - 2020 Jan-Dec
TI  - Phase I trial of dimethyl fumarate, temozolomide, and radiation therapy in 
      glioblastoma.
PG  - vdz052
LID - 10.1093/noajnl/vdz052 [doi]
LID - vdz052
AB  - BACKGROUND: Dimethyl fumarate (DMF), an oral agent approved for the treatment of 
      relapsing-remitting multiple sclerosis (RRMS), has promising preclinical activity 
      against glioblastoma (GBM). This phase I study sought to determine the 
      recommended phase 2 dose (RP2D) of DMF and evaluate its safety and toxicity when 
      combined with standard concurrent radiotherapy (RT) and temozolomide (TMZ) 
      followed by maintenance TMZ in patients with newly diagnosed GBM. METHODS: Using 
      a standard 3 + 3 dose-escalation design with 3 dose levels, patients received 
      daily DMF with 60 Gy RT and concurrent TMZ 75 mg/m(2) daily, followed by 
      maintenance DMF (continuously) and TMZ 150-200 mg/m(2) on days 1-5 of each 28-day 
      cycle for up to 6 cycles. The maximum tolerated dose (MTD) was determined by 
      evaluation of dose-limiting toxicity (DLT) during the first 6 weeks of therapy. 
      RESULTS: Twelve patients were treated at the 3 dose levels, and no DLTs were 
      observed. There were no unexpected toxicities. The most common grade 3/4 
      treatment related adverse events (AEs) were lymphopenia (58%), decreased CD4 
      count (17%), and thrombocytopenia (17%). Four patients completed all planned 
      treatment; seven patients had progression on treatment. One patient chose to 
      withdraw from the study during maintenance. The median progression-free survival 
      (PFS) for all patients was 8.7 months with no difference in PFS between those 
      with stable disease or a partial response; median overall survival was 13.8 
      months. CONCLUSIONS: DMF may be safely combined with RT and TMZ in patients with 
      newly diagnosed GBM. The RP2D for DMF is 240 mg three times daily.
CI  - (c) The Author(s) 2020. Published by Oxford University Press, the Society for 
      Neuro-Oncology and the European Association of Neuro-Oncology.
FAU - Shafer, Danielle
AU  - Shafer D
AD  - Inova Schar Cancer Institute, Fairfax, Virginia.
FAU - Tombes, Mary Beth
AU  - Tombes MB
AD  - Massey Cancer Center, Virginia Commonwealth University, Richmond, Virginia.
FAU - Shrader, Ellen
AU  - Shrader E
AD  - Massey Cancer Center, Virginia Commonwealth University, Richmond, Virginia.
FAU - Ryan, Alison
AU  - Ryan A
AD  - Massey Cancer Center, Virginia Commonwealth University, Richmond, Virginia.
FAU - Bandyopadhyay, Dipankar
AU  - Bandyopadhyay D
AD  - Massey Cancer Center, Virginia Commonwealth University, Richmond, Virginia.
FAU - Dent, Paul
AU  - Dent P
AD  - Massey Cancer Center, Virginia Commonwealth University, Richmond, Virginia.
FAU - Malkin, Mark
AU  - Malkin M
AD  - Department of Neurology, Massey Cancer Center, Virginia Commonwealth University, 
      Richmond, Virginia.
LA  - eng
PT  - Journal Article
DEP - 20200124
PL  - England
TA  - Neurooncol Adv
JT  - Neuro-oncology advances
JID - 101755003
PMC - PMC7212848
OTO - NOTNLM
OT  - dimethylfumurate
OT  - glioblastoma
OT  - radiation therapy
OT  - temozolomide
EDAT- 2020/07/10 06:00
MHDA- 2020/07/10 06:01
PMCR- 2020/01/24
CRDT- 2020/07/10 06:00
PHST- 2020/07/10 06:00 [entrez]
PHST- 2020/07/10 06:00 [pubmed]
PHST- 2020/07/10 06:01 [medline]
PHST- 2020/01/24 00:00 [pmc-release]
AID - vdz052 [pii]
AID - 10.1093/noajnl/vdz052 [doi]
PST - epublish
SO  - Neurooncol Adv. 2020 Jan 24;2(1):vdz052. doi: 10.1093/noajnl/vdz052. eCollection 
      2020 Jan-Dec.