PMID- 31844181
OWN - NLM
STAT- MEDLINE
DCOM- 20210308
LR  - 20231111
IS  - 1476-5608 (Electronic)
IS  - 1365-7852 (Print)
IS  - 1365-7852 (Linking)
VI  - 23
IP  - 2
DP  - 2020 Jun
TI  - A review of prostate cancer treatment impact on the CNS and cognitive function.
PG  - 207-219
LID - 10.1038/s41391-019-0195-5 [doi]
AB  - BACKGROUND: Androgen deprivation therapy (ADT) is the backbone of systemic 
      therapy for men with prostate cancer (PC); almost one-half of patients receive 
      treatment during their disease course. However, a range of cognitive and other 
      central nervous system (CNS) changes have been associated with ADT. In this 
      review, we discuss extant data describing these complications and the mechanisms 
      through which medications used to deliver ADT may affect them. METHODS: We 
      performed a MEDLINE search for appropriate papers published between January 2000 
      and December 2018. Relevant papers were selected and reviewed; additional 
      publications were identified by manually assessing references from included 
      papers, and recent congress abstracts. RESULTS: Of ~230 search outputs, 33 were 
      selected for inclusion. Some studies suggested a clear association between ADT 
      and CNS effects in men with PC, whereas others did not. Accurate assessment is 
      limited by test instrument variability, inadequate sample sizes, short follow-up 
      duration, and limited prospective longitudinal studies. The approved 
      second-generation androgen receptor (AR) inhibitors enzalutamide and apalutamide 
      were associated with some CNS-related adverse events (AEs) in clinical studies, 
      including fatigue (which can interfere with cognitive function). The androgen 
      synthesis inhibitor abiraterone acetate was associated with a low CNS AE profile 
      when compared with enzalutamide. The AR antagonist darolutamide demonstrated a 
      comparable incidence of cognitive disorder in clinical trials to that of ADT 
      alone. CONCLUSIONS: Adequately caring for men receiving ADT requires an 
      understanding of the symptoms, incidence and magnitude of cognitive effects, and 
      a feasible approach to cognitive assessment and management in clinical settings. 
      Some CNS effects could relate to blood-brain barrier penetration and direct AR 
      inhibitor activity; drug safety profiles may differ by the degree of blood-brain 
      barrier penetration of particular agents. Ongoing clinical trials seek to define 
      the CNS tolerability of newer AR pathway-targeted therapy options more clearly.
FAU - Ryan, Charles
AU  - Ryan C
AD  - Division of Hematology, Oncology and Transplantation, University of Minnesota, 
      Minneapolis, MN, USA. ryanc@umn.edu.
FAU - Wefel, Jeffrey S
AU  - Wefel JS
AD  - The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
FAU - Morgans, Alicia K
AU  - Morgans AK
AD  - Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20191216
PL  - England
TA  - Prostate Cancer Prostatic Dis
JT  - Prostate cancer and prostatic diseases
JID - 9815755
RN  - 0 (Androgen Antagonists)
SB  - IM
MH  - Androgen Antagonists/*therapeutic use
MH  - Central Nervous System/drug effects/*pathology
MH  - Cognition/*drug effects
MH  - Humans
MH  - Male
MH  - Meta-Analysis as Topic
MH  - Prognosis
MH  - Prostatic Neoplasms, Castration-Resistant/*drug therapy/pathology
PMC - PMC7237350
COIS- CR has received honoraria from Janssen, Bayer and Sanofi Aventis. JSW has acted 
      as a consultant for: Angiochem, Juno, Novocure, Vanquish Oncology and Magnolia 
      Tejas, and has been an Advisory Board member for: AbbVie, Bayer, Blueprint 
      Medicines, and Magnolia Neurosciences. AKM has received honoraria from 
      AstraZeneca, Astellas, Bayer, Janssen, Sanofi, Genentech, and Seattle Genetics, 
      and has received funding for an investigator-initiated study from Bayer.
EDAT- 2019/12/18 06:00
MHDA- 2021/03/09 06:00
PMCR- 2019/12/16
CRDT- 2019/12/18 06:00
PHST- 2019/07/08 00:00 [received]
PHST- 2019/11/18 00:00 [accepted]
PHST- 2019/11/07 00:00 [revised]
PHST- 2019/12/18 06:00 [pubmed]
PHST- 2021/03/09 06:00 [medline]
PHST- 2019/12/18 06:00 [entrez]
PHST- 2019/12/16 00:00 [pmc-release]
AID - 10.1038/s41391-019-0195-5 [pii]
AID - 195 [pii]
AID - 10.1038/s41391-019-0195-5 [doi]
PST - ppublish
SO  - Prostate Cancer Prostatic Dis. 2020 Jun;23(2):207-219. doi: 
      10.1038/s41391-019-0195-5. Epub 2019 Dec 16.