PMID- 29733524
OWN - NLM
STAT- MEDLINE
DCOM- 20191025
LR  - 20210109
IS  - 2045-7634 (Electronic)
IS  - 2045-7634 (Linking)
VI  - 7
IP  - 6
DP  - 2018 Jun
TI  - Safety and pharmacokinetics of veliparib extended-release in patients with 
      advanced solid tumors: a phase I study.
PG  - 2360-2369
LID - 10.1002/cam4.1488 [doi]
AB  - The poly(ADP-ribose) polymerase-1/2 inhibitor veliparib is active against tumors 
      deficient in homologous DNA damage repair. The pharmacokinetics and safety of 
      veliparib extended-release (ER) were evaluated in patients with advanced solid 
      tumors. This phase I study assessed veliparib-ER up to 800 mg once daily or 
      600 mg twice daily. Dose-limiting toxicities (DLTs), recommended phase II dose 
      (RP2D), and maximum tolerated dose (MTD) were assessed in cycle 1 and 
      safety/tolerability during continuous administration (28-day cycles). Seventy-one 
      patients (n = 53 ovarian, n = 17 breast, n = 1 prostate carcinoma) received 
      veliparib; 50 had deleterious breast cancer susceptibility (BRCA) gene mutations. 
      Single-dose veliparib-ER 200 mg (fasting) led to 58% lower peak concentration and 
      similar area under the concentration-time curve compared with veliparib 
      immediate-release (IR). Three patients experienced DLTs (grade 2: asthenia; grade 
      3: nausea/vomiting, seizure). RP2D and MTD for veliparib-ER were 400 mg BID. The 
      most frequent adverse events (AEs) were nausea (78.9%) and vomiting (50.7%). The 
      most common grade 3/4 treatment-related AEs were as follows: thrombocytopenia 
      (7.0%), nausea, and anemia (4.2% each). Overall, 12 (27.3%) patients with ovarian 
      and 10 (62.5%) patients with breast carcinoma had a partial response. 
      Veliparib-ER, versus veliparib-IR, exhibited an improved pharmacokinetic profile 
      and was well tolerated in patients with ovarian and BRCA-mutated breast cancers.
CI  - (c) 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
FAU - Werner, Theresa L
AU  - Werner TL
AUID- ORCID: 0000-0003-3868-7795
AD  - Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah.
FAU - Sachdev, Jasgit
AU  - Sachdev J
AD  - HonorHealth Research Institute, Scottsdale, Arizona.
FAU - Swisher, Elizabeth M
AU  - Swisher EM
AD  - University of Washington/Seattle Cancer Care Alliance, Seattle, Washington.
FAU - Gutierrez, Martin
AU  - Gutierrez M
AD  - John Theurer Cancer Center-Hackensack University Medical Center, Hackensack, New 
      Jersey.
FAU - Kittaneh, Muaiad
AU  - Kittaneh M
AD  - Loyola University Chicago, Maywood, Illinois.
FAU - Stein, Mark N
AU  - Stein MN
AD  - Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey.
FAU - Xiong, Hao
AU  - Xiong H
AD  - AbbVie Inc., North Chicago, Illinois.
FAU - Dunbar, Martin
AU  - Dunbar M
AD  - AbbVie Inc., North Chicago, Illinois.
FAU - Sullivan, Danielle
AU  - Sullivan D
AD  - AbbVie Inc., North Chicago, Illinois.
FAU - Komarnitsky, Philip
AU  - Komarnitsky P
AD  - AbbVie Inc., North Chicago, Illinois.
FAU - McKee, Mark
AU  - McKee M
AD  - AbbVie Inc., North Chicago, Illinois.
FAU - Tan, Antoinette R
AU  - Tan AR
AD  - Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey.
LA  - eng
SI  - ClinicalTrials.gov/NCT01853306
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20180507
PL  - United States
TA  - Cancer Med
JT  - Cancer medicine
JID - 101595310
RN  - 0 (Benzimidazoles)
RN  - 0 (Poly(ADP-ribose) Polymerase Inhibitors)
RN  - 01O4K0631N (veliparib)
SB  - IM
MH  - Adult
MH  - Benzimidazoles/pharmacokinetics/*therapeutic use
MH  - Breast Neoplasms/*drug therapy/pathology
MH  - Female
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Poly(ADP-ribose) Polymerase Inhibitors/pharmacology/*therapeutic use
PMC - PMC6010916
OTO - NOTNLM
OT  - BRCA
OT  - PARP inhibitor
OT  - breast carcinoma
OT  - extended-release formulation
OT  - ovarian carcinoma
OT  - veliparib
EDAT- 2018/05/08 06:00
MHDA- 2019/10/28 06:00
PMCR- 2018/05/07
CRDT- 2018/05/08 06:00
PHST- 2018/01/24 00:00 [received]
PHST- 2018/03/19 00:00 [revised]
PHST- 2018/03/20 00:00 [accepted]
PHST- 2018/05/08 06:00 [pubmed]
PHST- 2019/10/28 06:00 [medline]
PHST- 2018/05/08 06:00 [entrez]
PHST- 2018/05/07 00:00 [pmc-release]
AID - CAM41488 [pii]
AID - 10.1002/cam4.1488 [doi]
PST - ppublish
SO  - Cancer Med. 2018 Jun;7(6):2360-2369. doi: 10.1002/cam4.1488. Epub 2018 May 7.