PMID- 30131387
OWN - NLM
STAT- MEDLINE
DCOM- 20200226
LR  - 20200309
IS  - 1557-3265 (Electronic)
IS  - 1078-0432 (Print)
IS  - 1078-0432 (Linking)
VI  - 25
IP  - 1
DP  - 2019 Jan 1
TI  - Phase II Study of Iniparib with Concurrent Chemoradiation in Patients with Newly 
      Diagnosed Glioblastoma.
PG  - 73-79
LID - 10.1158/1078-0432.CCR-18-0110 [doi]
AB  - PURPOSE: Iniparib is a purported prodrug causing cell death through intracellular 
      conversion to nitro radical ions. We assessed the efficacy and safety of iniparib 
      with standard radiotherapy and temozolomide in patients with newly diagnosed 
      glioblastoma (GBM). PATIENTS AND METHODS: Adults meeting eligibility criteria 
      were enrolled in this prospective, single-arm, open-label multi- institution 
      phase II trial with median overall survival (mOS) compared with a historical 
      control as the primary objective. A safety run-in component of radiotherapy + 
      temozolomide + iniparib (n = 5) was followed by an efficacy study (n = 76) with 
      the recommended phase II doses of iniparib (8.0 mg/kg i.v. twice/week with 
      radiotherapy + daily temozolomide followed by 8.6 mg/kg i.v. twice/week with 
      5/28-day temozolomide). RESULTS: The median age of the 81 evaluable participants 
      was 58 years (63% male). Baseline KPS was >/= 80% in 87% of participants. The mOS 
      was 22 months [95% confidence interval (CI), 17-24] and the HR was 0.44 (95% CI, 
      0.35-0.55) per-person-year of follow-up. The 2- and 3-year survival rates were 
      38% and 25%, respectively. Treatment-related grade 3 adverse events (AEs) 
      occurred in 27% of patients; 9 patients had AEs requiring drug discontinuation 
      including infusion-related reaction, rash, gastritis, increased liver enzymes, 
      and thrombocytopenia. CONCLUSIONS: Iniparib is well tolerated with radiotherapy 
      and temozolomide in patients with newly diagnosed GBM at up to 17.2 mg/kg weekly. 
      The primary objective of improved mOS compared with a historical control was met, 
      indicating potential antitumor activity of iniparib in this setting. Dosing 
      optimization (frequency and sequence) is needed prior to additional efficacy 
      studies.
CI  - (c)2018 American Association for Cancer Research.
FAU - Blakeley, Jaishri O
AU  - Blakeley JO
AD  - Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, 
      Maryland. Jblakel3@jhmi.edu.
AD  - Department of Oncology and Neurosurgery, Johns Hopkins University School of 
      Medicine, Baltimore, Maryland.
FAU - Grossman, Stuart A
AU  - Grossman SA
AD  - Department of Oncology and Neurosurgery, Johns Hopkins University School of 
      Medicine, Baltimore, Maryland.
FAU - Chi, Andrew S
AU  - Chi AS
AD  - Laura and Isaac Perlmutter Cancer Center, New York University School of Medicine, 
      New York, New York.
FAU - Mikkelsen, Tom
AU  - Mikkelsen T
AD  - Ontario Brain Institute, Toronto, Ontario, Canada.
FAU - Rosenfeld, Myrna R
AU  - Rosenfeld MR
AUID- ORCID: 0000-0001-5095-2534
AD  - Institute for Biomedical Research (IDIBAPS)/Hospital Clinic, Barcelona, Spain.
FAU - Ahluwalia, Manmeet S
AU  - Ahluwalia MS
AD  - Brain Tumor and Neuro-Oncology Center, Cleveland Clinic, Cleveland, Ohio.
FAU - Nabors, L Burt
AU  - Nabors LB
AUID- ORCID: 0000-0001-5926-2230
AD  - Department of Neurology, University of Alabama at Birmingham, Birmingham, 
      Alabama.
FAU - Eichler, April
AU  - Eichler A
AD  - Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts.
FAU - Ribas, Ignacio Garcia
AU  - Ribas IG
AD  - Takeda Oncology, Cambridge, Massachusetts.
FAU - Desideri, Serena
AU  - Desideri S
AD  - Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, 
      Maryland.
FAU - Ye, Xiaobu
AU  - Ye X
AD  - Department of Oncology and Neurosurgery, Johns Hopkins University School of 
      Medicine, Baltimore, Maryland.
CN  - Adult Brain Tumor Consortium
LA  - eng
GR  - P30 CA006973/CA/NCI NIH HHS/United States
GR  - U01 CA062475/CA/NCI NIH HHS/United States
GR  - UM1 CA137443/CA/NCI NIH HHS/United States
GR  - U01 CA137443/CA/NCI NIH HHS/United States
GR  - T32 CA009574/CA/NCI NIH HHS/United States
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20180821
PL  - United States
TA  - Clin Cancer Res
JT  - Clinical cancer research : an official journal of the American Association for 
      Cancer Research
JID - 9502500
RN  - 0 (Benzamides)
RN  - 2ZWI7KHK8F (iniparib)
RN  - YF1K15M17Y (Temozolomide)
SB  - IM
MH  - Benzamides/*administration & dosage/adverse effects
MH  - Brain Neoplasms/*drug therapy/pathology
MH  - Chemoradiotherapy/adverse effects
MH  - Combined Modality Therapy
MH  - Female
MH  - Glioblastoma/*drug therapy/pathology
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Temozolomide/*administration & dosage/adverse effects
MH  - Treatment Outcome
PMC - PMC6367923
MID - NIHMS1504503
COIS- Conflict of Interest: The authors JOB, SAG, AC, TM, MRR, MSA, LBN, AE, SD, XY 
      declare no potential conflicts of interest. IGR was an employee of Sanofi at the 
      time of the design and launch of the study.
EDAT- 2018/08/23 06:00
MHDA- 2020/02/27 06:00
PMCR- 2020/01/01
CRDT- 2018/08/23 06:00
PHST- 2018/01/11 00:00 [received]
PHST- 2018/04/04 00:00 [revised]
PHST- 2018/08/16 00:00 [accepted]
PHST- 2018/08/23 06:00 [pubmed]
PHST- 2020/02/27 06:00 [medline]
PHST- 2018/08/23 06:00 [entrez]
PHST- 2020/01/01 00:00 [pmc-release]
AID - 1078-0432.CCR-18-0110 [pii]
AID - 10.1158/1078-0432.CCR-18-0110 [doi]
PST - ppublish
SO  - Clin Cancer Res. 2019 Jan 1;25(1):73-79. doi: 10.1158/1078-0432.CCR-18-0110. Epub 
      2018 Aug 21.