Lessening the impact of bone complications
Highlights from the Canadian Urological Association Annual Meeting, Montreal, June 2011
Bone loss and fractures
Men undergoing ADT for prostate cancer are at risk for bone loss (causing bone weakening) and fractures. In addition, in advanced, castrate-resistant prostate cancer (CRPC), the bones are a common site for the spread of cancer (metastasis). Several drugs are now available to prevent or reduce these bone complications.
Trials reporting on the effect of different oral bisphosphonates (drugs commonly used to treat osteoporosis) included one by Klotz and colleagues, which assessed a once-weekly dose of oral alendronate. The researchers found that this treatment prevented bone loss and increased bone mass in men with localized prostate cancer who were receiving ADT, with few side effects. The other study, by the Canadian Urologic Oncology Group, looked at the safety and effectiveness of oral risedronate compared to placebo in 140 men on ADT. After one year, risedronate was well tolerated and prevented bone loss at the lumbar spine. Which of the oral bisphosphonates doctors prescribe may depend partly on which ones are covered by provincial health plans as well as patients’ preference. Despite the benefits of these drugs, many men at risk for bone problems are still not taking these medications, or are not sticking with them.
Until now, there have been no data on the association of vertebral (spinal) fractures and mortality specifically in men with prostate cancer. To address this gap, Saad et al conducted an analysis of overall survival and vertebral fracture (assessed by spinal radiographs) in 1,486 men with nonmetastatic prostate cancer on ADT. These men were enrolled in a Phase III randomized controlled trial with denosumab, a new drug recently approved by Health Canada for men with prostate cancer-related bone metastases. After adjusting for age and length of time on ADT, there were more deaths in the group of men who had vertebral fractures at the beginning of the study (22% of participants) than in those with no fractures. The researchers concluded that men with fractures taking ADT seemed to have shorter overall survival.
Prolonging bone metastasis-free survival
Bone metastases can lead to bone pain and other debilitating effects. Another study evaluated the ability of denosumab to lengthen the time before bone metastases occur in men with CRPC. Men at high risk for developing bone metastases (PSA ≥8 and testosterone levels <50 ng/dL) were randomized to receive monthly injections of denosumab or placebo. Calcium and vitamin D supplements were also recommended. A total of 1,432 men participated in the study. The conclusion? Denosumab significantly improved bone metastasis-free survival, by 4.2 months compared with placebo, as well as the time to the first occurrence of a bone metastasis.
