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Genitourinary Cancers, Prostate Cancer
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Effects of Denosumab versus Zoledronic Acid in Patients with Castration-Resistant Prostate Cancer and Bone Metastases

Published Online: June 25th 2012 Oncology & Hematology Review (US), 2012;8(2):94-9 DOI: https://doi.org/10.17925/OHR.2012.08.2.94
Authors: Neal Shore, Carsten Goessl
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Abstract:
Overview

Progression of castration-resistant prostate cancer often leads to bone metastases, increasing the risk of skeletal-related events (SREs). The use of antiresorptive therapies such as denosumab, a human monoclonal antibody and zoledronic acid (ZA), a bisphosphonate, reduces bone destruction by inhibiting osteoclast function and survival. In 2002, ZA was approved for the prevention of skeletal complications in patients with bone disease from myeloma or bone metastases from solid tumors including prostate cancer. Recently, efficacy analysis demonstrated superiority of denosumab to ZA for the prevention or delay of SREs in 1,901 patients with prostate cancer and bone metastases, significantly delaying the time to first SRE and time to first and subsequent SRE compared to ZA. Decreases in bone turnover markers were greater with denosumab, mirroring the reduction in SREs. The reported incidence of adverse events were similar between denosumab and ZA. Advanced prostate cancer patients require long-term disease management where maintenance of overall bone health is an essential component of a comprehensive treatment program.

Keywords

Denosumab; zoledronic acid, prostate cancer; bone metastases; skeletal related events

Article:

Worldwide, prostate cancer is one of the most commonly diagnosed cancers in men. Approximately 900,000 new cases are reported each year with an estimated 242,000 cases in the US alone.1 Raised awareness leading to earlier detection and improved therapies have significantly extended life expectancy, as demonstrated by a decrease in US age-adjusted mortality of 3.7 % from 2004 to 2008.1 However, cause-specific mortality rates are still at approximately 32,000 patients per year. First-line treatments for advanced prostate cancer often include androgen deprivation therapy (ADT) which decrease serum testosterone levels, thus inhibiting prostate cancer cell growth and delaying disease progression.2 Initially, almost all advanced prostate cancer patients will respond to ADT with a reduction in prostate-specific antigen (PSA) in addition to radiographic regression. Nonetheless, biochemical and clinical responses to androgen deprivation are usually of limited duration. The castration-resistant cancer cells will proliferate and ultimately result in clinical progression. Castration-resistant prostate cancer (CRPC) can be broadly characterized as a progression of disease with an increase in PSA levels despite levels of testosterone less than 50 ng/dl.3,4 In comparison with castration-sensitive prostate cancer, the prognosis for CRPC patients is poor and survival is markedly reduced.5 Progression of CRPC often leads to bone metastases and skeletal-related events (SREs), leading to co-morbidities which may further reduce survival rates. Reported five-year survival rates for CRPC patients is 56 % without bone metastases, 3 % with bone metastases, and less than 1 % with bone metastases and SREs.6

Bone Metastases
For patients with advanced prostate cancer, the axial skeleton represents the most common site for metastases and approximately 90 % of all patients have evidence of bone metastases upon autopsy.7 In adults, the major sites for bone metastases are the vertebral column, pelvis, ribs, long bones, and skull,8 which also represent areas of active hematopoiesis.9 It has been postulated that these areas provide the primary tumor cells with a favorable environment for expansion and proliferation due to a high blood flow, nutrient-rich microenvironment with access to a large repository of growth factors often referred to as the ‘seed-and-soil’ hypothesis.10 By the end of life, the tumor load for the majority of patients will have shifted from the primary tumor to the bone. Batson demonstrated that venous blood from pelvic organs, like the prostate, directly flowed into the vertebral-venous (Batson’s) plexus.11

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Disclosure

Neal Shore, MD, FACS, is an employee of Atlantic Urology Clinics and has been a consultant for Amgen Inc, Astellas, Bayer, Dendreon, Janssen, Medivation, and Sanofi. Dr Shore has also been an Investigator for Biotech, BMS, Millenium, Oncogenix, Progenics, BN Immunotherapeutics. Carsten Goessl, MD, is an employee of Amgen Inc and currently owns Amgen Inc stock and stock options.

Correspondence

Neal Shore, MD, FACS, Medical Director, Carolina Urologic Research Center, 823 82nd Parkway, Myrtle Beach, SC 29572, US. E: nshore@grandstrandurology.com

Support

Medical writing support was provided by Albert Y Rhee, PhD, Amgen Inc.

Received

2012-08-06T00:00:00

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