PMID- 34427023
OWN - NLM
STAT- MEDLINE
DCOM- 20211221
LR  - 20211221
IS  - 1549-490X (Electronic)
IS  - 1083-7159 (Print)
IS  - 1083-7159 (Linking)
VI  - 26
IP  - 12
DP  - 2021 Dec
TI  - Phase I Study of Entinostat in Combination with Enzalutamide for Treatment of 
      Patients with Metastatic Castration-Resistant Prostate Cancer.
PG  - e2136-e2142
LID - 10.1002/onco.13957 [doi]
AB  - LESSONS LEARNED: Entinostat at the selected dose levels in combination with a 
      standard dose of enzalutamide showed a promising safety profile in this small 
      phase I study BACKGROUND: Entinostat inhibits prostate cancer (PCa) growth and 
      suppresses Treg cell function in vitro and in vivo. METHODS: This was a phase I 
      study to explore the safety and preliminary efficacy of entinostat (3 and 5 mg 
      orally per week) in combination with enzalutamide in castration resistant PCa 
      (CRPC). The study was carried out in an open-label two-cohort design. Patients 
      who had developed disease progression on or were eligible for enzalutamide were 
      enrolled in the study. The safety profile of the combination therapy, Prostate 
      specific antigen (PSA) levels, the pharmacokinetics of enzalutamide after 
      entinostat administration, peripheral T-cell subtype (including Treg 
      quantitation), and mononuclear cell (PBMC) histone H3 acetylation were analyzed. 
      RESULTS: Six patients with metastatic CRPC were enrolled. There was no noticeable 
      increment of fatigue related to entinostat. Toxicities possibly or probably 
      related to entinostat or the combination therapy included grade 3 anemia 1/6 
      (17%), grade 2 white blood cell (WBC) decrease 1/6 (17%), and other self-limiting 
      grade 1 adverse events (AEs). Median duration of treatment with entinostat was 
      18 weeks. Entinostat did not affect the steady plasma concentration of 
      enzalutamide. Increased PBMC histone H3 acetylation was observed in blood 
      samples. No evident T-cell subtype changes were detected, including in Treg 
      quantitation. CONCLUSION: Entinostat 5 mg weekly in combination with enzalutamide 
      showed an acceptable safety profile in this small phase I study. A planned phase 
      II part of the trial was terminated because of sponsor withdrawal.
CI  - (c) AlphaMed Press; the data published online to support this summary are the 
      property of the authors.
FAU - Lin, Jianqing
AU  - Lin J
AUID- ORCID: 0000-0002-0406-690X
AD  - Department of Medicine, George Washington University School of Medicine and 
      Health Sciences, Washington, DC, USA.
FAU - Elkon, Jacob
AU  - Elkon J
AD  - Department of Medicine, George Washington University School of Medicine and 
      Health Sciences, Washington, DC, USA.
FAU - Ricart, Brittany
AU  - Ricart B
AD  - Department of Medicine, George Washington University School of Medicine and 
      Health Sciences, Washington, DC, USA.
FAU - Palmer, Erica
AU  - Palmer E
AD  - Department of Medicine, George Washington University School of Medicine and 
      Health Sciences, Washington, DC, USA.
FAU - Zevallos-Delgado, Christian
AU  - Zevallos-Delgado C
AD  - Department of Medicine, George Washington University School of Medicine and 
      Health Sciences, Washington, DC, USA.
FAU - Noonepalle, Satish
AU  - Noonepalle S
AD  - Department of Medicine, George Washington University School of Medicine and 
      Health Sciences, Washington, DC, USA.
FAU - Burgess, Brooke
AU  - Burgess B
AD  - Department of Medicine, George Washington University School of Medicine and 
      Health Sciences, Washington, DC, USA.
FAU - Siegel, Robert
AU  - Siegel R
AD  - Department of Medicine, George Washington University School of Medicine and 
      Health Sciences, Washington, DC, USA.
FAU - Ma, Yan
AU  - Ma Y
AD  - Department of Medicine, George Washington University School of Medicine and 
      Health Sciences, Washington, DC, USA.
FAU - Villagra, Alejandro
AU  - Villagra A
AD  - Department of Medicine, George Washington University School of Medicine and 
      Health Sciences, Washington, DC, USA.
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
DEP - 20210914
PL  - England
TA  - Oncologist
JT  - The oncologist
JID - 9607837
RN  - 0 (Benzamides)
RN  - 0 (Nitriles)
RN  - 0 (Pyridines)
RN  - 1ZNY4FKK9H (entinostat)
RN  - 2010-15-3 (Phenylthiohydantoin)
RN  - 93T0T9GKNU (enzalutamide)
SB  - IM
MH  - Benzamides
MH  - Humans
MH  - Leukocytes, Mononuclear
MH  - Male
MH  - Nitriles
MH  - Phenylthiohydantoin
MH  - *Prostatic Neoplasms, Castration-Resistant/drug therapy
MH  - Pyridines
PMC - PMC8649040
OTO - NOTNLM
OT  - Combination
OT  - Entinostat
OT  - Enzalutamide
OT  - Prostate cancer
EDAT- 2021/08/25 06:00
MHDA- 2021/12/22 06:00
PMCR- 2021/12/01
CRDT- 2021/08/24 06:34
PHST- 2021/04/14 00:00 [received]
PHST- 2021/08/14 00:00 [accepted]
PHST- 2021/08/25 06:00 [pubmed]
PHST- 2021/12/22 06:00 [medline]
PHST- 2021/08/24 06:34 [entrez]
PHST- 2021/12/01 00:00 [pmc-release]
AID - ONCO13957 [pii]
AID - 10.1002/onco.13957 [doi]
PST - ppublish
SO  - Oncologist. 2021 Dec;26(12):e2136-e2142. doi: 10.1002/onco.13957. Epub 2021 Sep 
      14.