The role of bisphosphonates or denosumab in light of the availability of new therapies for prostate cancer.

Abstract

Most men with advanced prostate cancer will develop bone metastases, which have a substantial impact on quality of life. Bone metastases can lead to skeletal-related events (SREs), which place a burden on patients and healthcare systems. For men with castration-resistant prostate cancer (CRPC) and bone metastases, the treatment landscape has evolved rapidly over the past few years. The relatively recent approvals of the hormonal agents abiraterone acetate and enzalutamide, second-line chemotherapy cabazitaxel, and the radiopharmaceutical radium-223 dichloride (radium-223), have provided clinicians with a greater choice of treatments. These compounds have benefits in terms of overall survival based on the results of pivotal phase 3 studies. The bisphosphonate zoledronic acid and the RANK ligand inhibitor denosumab are indicated for the prevention of SREs in men with metastatic CRPC but studies of these compounds have not demonstrated a survival benefit. The important question of the role of bisphosphonates or denosumab in combination with these new agents has thus materialised. Current and emerging evidence from clinical studies of abiraterone acetate, enzalutamide and radium-223, suggest that addition of bisphosphonates or denosumab to these new therapies may provide further clinical benefits for patients with prostate cancer and bone metastases. This evidence may help to shape clinical practice but are based largely on post hoc analyses of clinical trial data. It is therefore apparent that further data are required from both clinical studies and real-world settings to enable physicians to understand the efficacy and safety of combination therapy with the new agents plus bisphosphonates or denosumab.

• Authors: Fred Saad, Cora N Sternberg, Peter F A Mulders, Daniela Niepel, Bertrand F Tombal
• Journal: Cancer treatment reviews (Cancer Treat Rev) Vol. 68 Pg. 25-37 (Jul 2018) ISSN: 1532-1967 [Electronic] Netherlands
• PMID: 29787892 (Publication Type: Journal Article, Review)
• Copyright: Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Chemical References

• Benzamides
• Bone Density Conservation Agents
• Diphosphonates
• Imidazoles
• Nitriles
• Radioisotopes
• Taxoids
• Phenylthiohydantoin
• Denosumab
• cabazitaxel
• Zoledronic Acid
• enzalutamide
• Abiraterone Acetate
• radium Ra 223 dichloride
• Radium

Topics

• Abiraterone Acetate (administration & dosage)
• Benzamides
• Bone Density Conservation Agents (administration & dosage)
• Bone Neoplasms (drug therapy, secondary)
• Clinical Trials, Phase III as Topic
• Denosumab (administration & dosage)
• Diphosphonates (administration & dosage)
• Humans
• Imidazoles (administration & dosage)
• Male
• Nitriles
• Phenylthiohydantoin (administration & dosage, analogs & derivatives)
• Prostatic Neoplasms, Castration-Resistant (pathology, therapy)
• Radioisotopes (administration & dosage)
• Radium (administration & dosage)
• Randomized Controlled Trials as Topic
• Taxoids (administration & dosage)
• Zoledronic Acid