How protein inhibition delays bone metastases Researchers in France have uncovered the mystery of how the onset of bone metastases can be postponed. Speaking at the recent 2011 European Multidisciplinary Cancer Congress in Stockholm, Sweden, Professor Stéphane Oudard from the Department of Oncology at the Georges Pompidou... Researchers in France have uncovered the mystery of how the onset of bone metastases can be postponed. Speaking at the recent 2011 European Multidisciplinary Cancer Congress in Stockholm, Sweden, Professor Stéphane Oudard from the Department of Oncology at the Georges Pompidou Hospital in France pointed out that inhibiting a protein involved in bone metabolism is key in delaying bone metastases, a common occurrence in men diagnosed with a particular form of prostate cancer. Professor Oudard noted that the research carried out by his team on the effects of the monoclonal antibody denosumab (XGEVA TM) is the first large-scale clinical trial to demonstrate such an effect. Up to 90% of men with prostate cancer that cannot be treated with hormones will have their primary tumour metastasise to bone, according to the European CanCer Organisation (ECCO). When metastases begin, it usually signifies that the cancer is entering a chronic phase, and then a terminal phase. Ultimately, the patient faces both physical and psychological challenges including fractures and spinal cord compression. 'Being able to delay this turning point is therefore very significant,' Professor Oudard said. 'We have shown that the use of denosumab in this group of patients can impede the onset of bone metastases by just over four months.' Inhibited by the drug, the RANKL protein plays a crucial role in forming osteoclasts. Compared with osteoblasts that form bone, osteoclasts do the opposite by destroying bone. By thwarting the formation of osteoclasts, we can stop the destruction of bone and strengthen its ability to fight metastases development. A total of 1,432 male subjects were tested, randomised into 1 of 2 groups: one group received the active drug and the other received the placebo. All subjects were encouraged to take calcium and vitamin D supplements for bone health. In July 2010, the researchers found that over 660 of the patients had either developed bone metastases or had died. The team unblinded the trial and evaluated the results. 'We found that denosumab prolonged bone metastasis-free survival significantly as compared with placebo, and that these results were consistent among different sub-groups of the disease and demographic variables such as age, ethnicity, and geographical location,' Professor Oudard said. 'From this we can conclude that, whatever the patient characteristics (initially based on a high prostate specific antigen (PSA) value and/or a short PSA doubling time), denosumab can delay the appearance of bone metastasis. In a condition where there is currently no effective treatment, this is a highly significant finding.' The data show that patients with bone metastases have a five-fold greater risk of dying versus patients without bone metastases. 'Effective therapies are already in place for both early (hormone-sensitive) and advanced (hormone-resistant) prostate cancer, but until now there was a gap in the treatment plan for this group of patients, who are hormone-resistant but have not yet developed metastatic disease,' Prof Oudard says. 'Our trial has shown that denosumab prolongs the period before metastasis where the patients' quality of life has not yet suffered to a great extent. For the first time, we have shown that targeting the bone micro-environment can work in this way. We believe that in future we may be able to do even better by combining denosumab with other targeted treatments.' Commenting on the results of the study, ECCO President Professor Michael Baumann said: 'This is the first large clinical trial to demonstrate that targeting of the bone micro-environment significantly delays onset of bone metastases in hormone resistant prostate cancer patients with high risk for development of bone metastases. What is really striking here is that the effect holds true for all sub-groups of patients evaluated. This offers new options for a considerable group of patients and also will stimulate important further research in this field.'For more information, please visit:European CanCer Organisation (ECCO):http://www.ecco-org.eu/ Countries France, Sweden
