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2017 ; 9
(3-4
): 81-88
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gab.com Text
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Denosumab treatment in the management of patients with advanced prostate cancer:
clinical evidence and experience
#MMPMID28392837
Hegemann M
; Bedke J
; Stenzl A
; Todenhöfer T
Ther Adv Urol
2017[Mar]; 9
(3-4
): 81-88
PMID28392837
show ga
Osteoprotective therapies have become an essential component in the management of
advanced prostate cancer (PC) patients as bone metastases (BMs) have a major
impact on morbidity and mortality. Denosumab is a fully humanized antibody
targeting the receptor activator of nuclear factor ?B ligand (RANKL), which has
been approved by the European Medicines Agency (EMA) in Europe and the United
States (US) Food and Drug Administration (FDA) in the US for prevention of
skeletal-related events (SREs) in patients with solid tumors and BMs, including
PC. The clinical settings in which PC patients should be treated with denosumab
are still discussed controversially. In a phase III study, denosumab
significantly delayed SREs compared with zoledronic acid (ZA) in patients with
metastatic castration-resistant PC (CRPC). In addition, denosumab showed superior
effects on pain and health-related quality of life (QoL) in these patients. In
patients with nonmetastatic CRPC, denosumab has been proven to significantly
increase bone metastases-free survival. However, no significant benefits on
cancer-specific and overall survival were observed and denosumab was not approved
by the US FDA and EMA in this context. The effectiveness of denosumab in patients
with castration-sensitive PC (CSPC) and BMs is also under discussion, as clinical
trials with ZA in these patients have not shown significant benefits. Clinical
data on the use of denosumab in CSPC are urgently needed.