PMID- 24764124
OWN - NLM
STAT- MEDLINE
DCOM- 20150609
LR  - 20211122
IS  - 1573-0646 (Electronic)
IS  - 0167-6997 (Print)
IS  - 0167-6997 (Linking)
VI  - 32
IP  - 5
DP  - 2014 Oct
TI  - Targeting DNA repair with combination veliparib (ABT-888) and temozolomide in 
      patients with metastatic castration-resistant prostate cancer.
PG  - 904-12
LID - 10.1007/s10637-014-0099-0 [doi]
AB  - Androgen receptor-mediated transcription is directly coupled with the induction 
      of DNA damage, and castration-resistant tumor cells exhibit increased activity of 
      poly (ADP-ribose) polymerase (PARP)-1, a DNA repair enzyme. This study assessed 
      the efficacy and safety of low dose oral PARP inhibitor veliparib (ABT-888) and 
      temozolomide (TMZ) in docetaxel-pretreated patients with metastatic 
      castration-resistant prostate cancer (mCRPC) in a single-arm, open-label, pilot 
      study. Patients with mCRPC progressing on at least one docetaxel-based therapy 
      and prostate specific antigen (PSA) >/= 2 ng/mL were treated with veliparib 40 mg 
      twice daily on days 1-7 and TMZ once daily (150 mg/m(2)/day cycle 1; if well 
      tolerated then 200 mg/m(2)/day cycle 2 onwards) on days 1-5 q28 days. Patients 
      received 2 (median) treatment cycles (range, 1-9). The primary endpoint was 
      confirmed PSA response rate (decline >/= 30 %). Twenty-six eligible patients were 
      enrolled, 25 evaluable for PSA response. Median baseline PSA was 170 ng/mL. Two 
      patients had a confirmed PSA response (8.0 %; 95 % CI: 1.0-26.0), 13 stable PSA, 
      and 10 PSA progression. The median progression-free survival was 9 weeks (95 % 
      CI: 7.9-17) and median overall survival 39.6 weeks (95 % CI: 26.6-not estimable). 
      The most frequent treatment-emergent adverse events (AEs) were thrombocytopenia 
      (77 %), anemia (69 %), fatigue (50 %), neutropenia (42 %), nausea (38 %), and 
      constipation (23 %). Grade 3/4 AEs occurring in > 10 % of patients were 
      thrombocytopenia (23 %) and anemia (15 %). Veliparib and TMZ combination was well 
      tolerated but with modest activity. Biomarker analysis supported the proof of 
      concept that this combination has some antitumor activity in mCRPC.
FAU - Hussain, Maha
AU  - Hussain M
AD  - Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI, USA, 
      mahahuss@med.umich.edu.
FAU - Carducci, Michael A
AU  - Carducci MA
FAU - Slovin, Susan
AU  - Slovin S
FAU - Cetnar, Jeremy
AU  - Cetnar J
FAU - Qian, Jiang
AU  - Qian J
FAU - McKeegan, Evelyn M
AU  - McKeegan EM
FAU - Refici-Buhr, Marion
AU  - Refici-Buhr M
FAU - Chyla, Brenda
AU  - Chyla B
FAU - Shepherd, Stacie P
AU  - Shepherd SP
FAU - Giranda, Vincent L
AU  - Giranda VL
FAU - Alumkal, Joshi J
AU  - Alumkal JJ
LA  - eng
SI  - ClinicalTrials.gov/NCT01085422
GR  - P30 CA006973/CA/NCI NIH HHS/United States
PT  - Clinical Trial
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20140426
PL  - United States
TA  - Invest New Drugs
JT  - Investigational new drugs
JID - 8309330
RN  - 0 (Benzimidazoles)
RN  - 0 (Poly(ADP-ribose) Polymerase Inhibitors)
RN  - 01O4K0631N (veliparib)
RN  - 7GR28W0FJI (Dacarbazine)
RN  - EC 3.4.21.- (KLK3 protein, human)
RN  - EC 3.4.21.- (Kallikreins)
RN  - EC 3.4.21.77 (Prostate-Specific Antigen)
RN  - YF1K15M17Y (Temozolomide)
SB  - IM
MH  - Aged
MH  - Aged, 80 and over
MH  - Antineoplastic Combined Chemotherapy Protocols/adverse 
      effects/pharmacology/*therapeutic use
MH  - Benzimidazoles/administration & dosage/adverse effects
MH  - DNA Repair/drug effects
MH  - Dacarbazine/administration & dosage/adverse effects/analogs & derivatives
MH  - Humans
MH  - Kallikreins/blood
MH  - Male
MH  - Middle Aged
MH  - Pilot Projects
MH  - Poly(ADP-ribose) Polymerase Inhibitors
MH  - Prostate-Specific Antigen/blood
MH  - Prostatic Neoplasms, Castration-Resistant/blood/*drug therapy
MH  - Temozolomide
MH  - Treatment Outcome
PMC - PMC4659356
MID - NIHMS737143
COIS- Conflict of interest Jiang Qian, Evelyn McKeegan, Marion Refici-Buhr, Brenda 
      Chyla. Stacie Shepherd and Vincent Giranda are employees and stock owners of 
      AbbVie. Maha Hussain, Michael Carducci, Susan Slovin, Jeremy Cetnar, and Joshi 
      Alumkal have no conflicts to disclose.
EDAT- 2014/04/26 06:00
MHDA- 2015/06/10 06:00
PMCR- 2015/11/25
CRDT- 2014/04/26 06:00
PHST- 2013/12/18 00:00 [received]
PHST- 2014/03/30 00:00 [accepted]
PHST- 2014/04/26 06:00 [entrez]
PHST- 2014/04/26 06:00 [pubmed]
PHST- 2015/06/10 06:00 [medline]
PHST- 2015/11/25 00:00 [pmc-release]
AID - 10.1007/s10637-014-0099-0 [doi]
PST - ppublish
SO  - Invest New Drugs. 2014 Oct;32(5):904-12. doi: 10.1007/s10637-014-0099-0. Epub 
      2014 Apr 26.