WASHINGTON (February 25, 2011) – Prostate cancer in men usually becomes resistant to initial hormone treatment within a few years of diagnosis (and is thereafter called castration-resistant prostate cancer) and tumors begin to grow again and spread to other parts of the body (metastasis), including bones. This increases the risk of bone breakages and other bone events that cause significant disability and quality of life issues. An article by Professor Karim Fizazi, Department of Cancer Medicine, University of Paris Sud, France, and colleagues, published online by The Lancet, shows that a new drug denosumab is better than the current standard treatment of zoledronic acid for delaying and preventing bone events in men with castration-resistant prostate cancer.
Denosumab works by inhibiting the RANKL gene, which then lowers activity of the body’s osteoclast cells responsible for re-absorbing (and therefore weakening) bone; zoledronic acid also inhibits osteoclasts but using a different mechanism.
The authors say: “Therapeutic intervention targeting the RANKL pathway is a recent strategy in the management of skeletal complications of metastatic disease: denosumab is the first monoclonal antibody to be investigated for this purpose.”
In a linked comment, Jeanny Aragon-Ching, M.D. assistant professor of Medicine at The George Washington University School of Medicine and Health Sciences, says that denosumab is a welcome addition to the options available for treatment of metastatic prostate cancer. She adds that since pain and fatigue were commonly reported in both groups, reports on how each drug affects quality of life would be informative.
“As with other agents that have been successful in the metastatic setting, moving this drug towards early stages of disease is the logical next step in identification of its other potential uses,” says Dr. Aragon-Ching. “Denosumab has already been shown to reduce skeletal fractures in men who are undergoing androgen-deprivation therapy without overt clinical metastasis. Clinical trials assessing the use of denosumab in the delay of onset of metastasis have been promising and will help further define its role in prostate cancer.”
Read the abstract of "Denosumab versus zoledronic acid for treatment of bone metastases in men with castration-resistant prostate cancer: a randomised, double-blind study" at The Lancet.
