[The clinical merit of anti-RANKL antibody denosumab in prostate cancer].

Abstract

Prostate cancer has been reported to have a high bone metastatic rate and longer survival duration by current therapies, accordingly, the treatment for bone metastasis is important to maintain a good quality of life. The standard medication for advanced prostate cancer, androgen deprivation therapy(ADT)has been associated with bone loss, consequently, the management of controlling the risk of fracture is required. A new drug denosumab is a fully human monoclonal antibody that binds to RANKL, a cytokine essential for the differentiation, function, and survival of osteoclasts which mainly regulate bone metabolic turnover. In a phase 3 clinical study in patients with bone metastasis of castrate-resistant prostate cancer, 120 mg denosumabsub cutaneously every 4 weeks statistically significantly delayed the time to first skeletal-related events(SRE)by 18% and also the time to first and subsequent on-study SRE by 18%when compared with that of the standard of care, 4 mg zoledronic acid by iv infusion every 4 weeks. In another phase 3 clinical study in patients with castrate-resistant prostate cancer without bone metastases, 120 mg once in 4-week subcutaneous injection of denosumab has been indicated to delay the onset of the bone metastasis significantly when compared with placebo. In another phase 3 clinical study in patients with hormone-sensitive nonmetastatic prostate cancer, 60 mg denosumab subcutaneously every 6 months significantly reversed bone loss due to ADT and demonstrated statistically significant prevention of vertebral fractures compared with placebo. Based on these evidences, it has been proved that denosumab is effective in many different stages across the disease continuum of advanced prostate cancer. In US, denosumab has been approved for the indication of prevention of SRE caused by bone metastasis of solid tumor since 2010. Denosumab is useful for treatment of bone metastases from prostate cancer, because the administration route is an every 4-week subcutaneous injection and, dose adjustment by renal impairment is not required. The use of denosumab will be expected to largely contribute to prostate cancer treatment in the future.

• Authors: Hideyuki Akaza, Taiji Tsukamoto, Kazuhiro Suzuki, Mikio Namiki, Seiichiro Ozono, Seiji Naitodept
• Journal: Gan to kagaku ryoho. Cancer & chemotherapy (Gan To Kagaku Ryoho) Vol. 39 Issue 2 Pg. 207-12 (Feb 2012) ISSN: 0385-0684 [Print] Japan
• PMID: 22333629 (Publication Type: English Abstract, Journal Article)

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• RANK Ligand
• Denosumab

Topics

• Animals
• Antibodies, Monoclonal (therapeutic use)
• Antibodies, Monoclonal, Humanized
• Bone Neoplasms (drug therapy, prevention & control, secondary)
• Denosumab
• Humans
• Male
• Prostatic Neoplasms (drug therapy, pathology)
• RANK Ligand (antagonists & inhibitors, metabolism)
• Signal Transduction (drug effects)