Changing Fate of Bone-Related Therapies for Prostate Cancer

Prostate cancer is the third leading cause of death from cancer among men, yet one of the more troubling concerns regarding the disease is that the cancer metastasizes to the bone in approximately 90% of advanced cases. After a few clinical trials failed to find a therapy that helped patients, two trials are underway that not only address bone-related issues, but might improve survival rates for patients.

One study involved denosumab, a drug that is used to treat a number of bone-related issues, including bone loss, rheumatoid arthritis, and bone metastases. In a study released in 2010, denosumab delayed the median time for the development of metastasis by 4.2 months in men who had castration-resistant prostate cancer with no bone metastasis at the time of enrollment but who were considered high risk for developing bone metastasis.

Another study, involving alpharadin, a particle-emitting isotope of radium, also reported encouraging results. This ongoing phase III clinical trial included 922 patients with both castration-resistant prostate cancer and symptomatic bone metastases. The interim analysis showed that patients taking alpharadin had a median survival of 14 months compared to 11.2 months in patients receiving the placebo.

Daniel Petrylak, MD

“Not only did patients respond to the drug, but alpharadin appeared to improve their survival as well,” said Daniel Petrylak, MD, Professor of Medicine and Co-Leader of Prostate Cancer in the Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center. Further results on alpharadin were released at the European Multidisciplinary Cancer Congress, showing that the drug was associated with a 30% reduction in the odds of dying from prostate cancer.

The results of the denosumab and alpharadin studies may change the fate of bone-related therapies for prostate cancer. Abbott Laboratories has struggled with their drug atrasentan. After showing promising results in a phase II clinical trial, the same could not be said of phase III clinical trials. After the FDA denied approval of the drug as a monotherapy for advanced prostate cancer, Abbott sought approval for the drug in combination with chemotherapy. Earlier this year, however, a phase III clinical trial was terminated after the drug showed no survival benefit when combined with docetaxel and prednisone.

“Atrasentan is basically finished at this point,” Petrylak said.

Petrylak said that although the data is exciting and potentially practice changing, there is much more work that needs to be done in terms of understanding the biology behind prostate cancer and its propensity for metastasizing in the bones, as well as the mechanism of action of these drugs.