49IN - How should we utilize bone treatments: Bisphosphonates, denosumab and radium-223
|Date||30 September 2012|
|Event||ESMO Congress 2012|
|Session||Re-inventing the medical treatment of advanced prostate cancer|
|Topics|| Supportive Care
How should we utilize bone treatments: Bisphosphonates, denosumab and radium-223? Bone metastases are a prominent feature of CRPC, and can lead to significant skeletal-related events (SREs) such as spinal cord compression, pathological fracture, and the need for surgery or external-beam radiotherapy. Zoledronate, a bisphosphonate, reduces the risk of SREs (1) and has been widely, although not universally, regarded as a standard treatment for metastatic CRPC. More recently, denosumab, an antibody targeted at the RANK-ligand, has shown greater efficacy for SRE prevention with an acceptable toxicity profile (2), and has also been licensed for use. Radium-223, a bone-targetted alpha emitter, has been reported not only to reduce the risk of SREs, but also to improve overall survival. Although radium-223 is the first bone-targetted agent to improve overall survival in CRPC, it is not yet licensed for clinical use. I will review the clinical trial data concerning these bone-targetted agents in CRPC, and give my personal view as to how they should be used.
References 1. A randomized, placebo-controlled trial of zoledronic acid in patients with hormone-refractory metastatic prostate carcinoma. Saad F, Gleason DM, Murray R, Tchekmedyian S, Venner P, Lacombe L, Chin JL, Vinholes JJ, Goas JA, Chen B; Zoledronic Acid Prostate Cancer Study Group. J Natl Cancer Inst. 2002 Oct 2;94(19):1458-68. 2. Denosumab versus zoledronic acid for treatment of bone metastases in men with castration-resistant prostate cancer: a randomised, double-blind study. Fizazi K, Carducci M, Smith M, Damião R, Brown J, Karsh L, Milecki P, Shore N, Rader M, Wang H, Jiang Q, Tadros S, Dansey R, Goessl C. Lancet. 2011 Mar 5;377(9768):813-22. 3. Overall survival benefit of radium-223 chloride (Alpharadin™) in the treatment of patients with symptomatic bone metastases in castration-resistant prostate cancer (CRPC): A phase III randomized trial (ALSYMPCA). C. Parker, D. Heinrich, J.M. O'Sullivan, S. Fosså, A. Chodacki, T. Demkow, A. Cross, B. Bolstad, J. Garcia-Vargas, and O. Sartor. Eur J Cancer 47:Supp 2, Sept 2011 p3Disclosure
C. Parker: Advisory board membership for Amgen, BMS, Bayer, Dendreon, Janssen and Takeda