PMID- 22751146
OWN - NLM
STAT- MEDLINE
DCOM- 20130809
LR  - 20220316
IS  - 1476-5608 (Electronic)
IS  - 1365-7852 (Linking)
VI  - 16
IP  - 1
DP  - 2013 Mar
TI  - New considerations for ADT in advanced prostate cancer and the emerging role of 
      GnRH antagonists.
PG  - 7-15
LID - 10.1038/pcan.2012.25 [doi]
AB  - Androgen deprivation therapy (ADT) is first-line treatment for metastatic 
      prostate cancer (PCa). Gonadotrophin-releasing hormone (GnRH) agonists are the 
      most commonly used ADT but have several theoretical physiologic disadvantages 
      (e.g. initial testosterone surge, potential microsurges upon repeat 
      administration). Testosterone surge delays the intended serologic endpoint of 
      testosterone suppression and may exacerbate clinical symptoms. GnRH antagonists 
      were developed with a view toward overcoming these potential adverse physiologic 
      events. This review evaluates GnRH agonists and antagonists, assessing the 
      potential future role of antagonists in PCa and strategies to minimize ADT 
      adverse events (AEs). Evidence was identified via PubMed search (by GnRH agent 
      and other ADT-related terms), from review article bibliographies, and authors' 
      therapy area knowledge, with articles included by author consensus. Degarelix 
      shows similar efficacy to a GnRH agonist in achieving and maintaining castration, 
      with faster onset and without testosterone surge/microsurges. Phase III data 
      showed that, in the first treatment year, degarelix displayed a lower risk of PSA 
      failure or death (composite endpoint), lower levels of the bone marker serum 
      alkaline phosphatase (in baseline metastatic disease), and fewer musculoskeletal 
      AEs than the agonist leuprolide. Also, crossing over from leuprolide to degarelix 
      after 1 year reduced the risk of PSA failure or death. ADT displays an AE 
      spectrum which can impact quality of life as well as causing significant 
      morbidities. Strategies to improve ADT tolerability have become increasingly 
      important including: a holistic management approach, improved diet and exercise, 
      more specific monitoring to detect and prevent testosterone depletion toxicities, 
      and intermittent ADT allowing hormonal recovery between treatment periods. 
      Clinical studies suggest possible benefits of GnRH antagonists over agonists 
      based on different mechanisms of action. GnRH antagonists should now be 
      considered as an alternative first-line ADT option in advanced PCa. Intermittent 
      ADT and a holistic treatment approach are promising strategies to improve ADT 
      tolerability.
FAU - Shore, N D
AU  - Shore ND
AD  - Carolina Urologic Research Center, Myrtle Beach, SC 29572, USA. 
      nshore@grandstrandurology.com
FAU - Abrahamsson, P-A
AU  - Abrahamsson PA
FAU - Anderson, J
AU  - Anderson J
FAU - Crawford, E D
AU  - Crawford ED
FAU - Lange, P
AU  - Lange P
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20120703
PL  - England
TA  - Prostate Cancer Prostatic Dis
JT  - Prostate cancer and prostatic diseases
JID - 9815755
RN  - 0 (Androgen Antagonists)
RN  - 0 (Antineoplastic Agents)
RN  - 33515-09-2 (Gonadotropin-Releasing Hormone)
SB  - IM
MH  - Androgen Antagonists/*therapeutic use
MH  - Antineoplastic Agents/*therapeutic use
MH  - Clinical Trials as Topic
MH  - Gonadotropin-Releasing Hormone/*antagonists & inhibitors
MH  - Humans
MH  - Male
MH  - Prostatic Neoplasms/*drug therapy
EDAT- 2012/07/04 06:00
MHDA- 2013/08/10 06:00
CRDT- 2012/07/04 06:00
PHST- 2012/07/04 06:00 [entrez]
PHST- 2012/07/04 06:00 [pubmed]
PHST- 2013/08/10 06:00 [medline]
AID - pcan201225 [pii]
AID - 10.1038/pcan.2012.25 [doi]
PST - ppublish
SO  - Prostate Cancer Prostatic Dis. 2013 Mar;16(1):7-15. doi: 10.1038/pcan.2012.25. 
      Epub 2012 Jul 3.