Advances in Treatment for Bone Metastases

Recently, bisphosphonates have become attractive treatments for preventing pathological fractures and relieving bone pain from metastases. The goal of treatment for bone metastases is palliative, to relieve pain and risk of fracture, and has historically consisted of surgery, radiation therapy, and pain medications. Bisphosphonate drugs, a newer approach to treatment for bone metastases, can effectively prevent loss of bone that occurs from metastatic lesions, reduce the risk of fractures, and decrease pain.

Bisphosphonate drugs inhibiting bone resorption, or break-down. Bone is constantly being "remodeled" by two types of cells: osteoclasts, which break down bone, and osteoblasts, which rebuild bone.

Although the exact process by which bisphosphonates work is not completely understood, it is thought that bisphosphonates inhibit osteoclasts and induce apoptosis (cell death) in these cells. There is also evidence that these drugs bind to bone, thereby blocking osteoclastic resorption.

Cancer cells release various factors that stimulate osteoclastic activity, causing increased breakdown of bone. By inhibiting osteoclasts, bisphosphonate drugs effectively reduce the detrimental impact that cancer cells have on bone density. Clinical trials have demonstrated the activity of two new bisphosphonate drugs in cancer patients: Zometa® and Aredia®.

Bisphosphonates can effectively prevent or delay bone destruction and related pain. This activity has been demonstrated in clinical trials with multiple myeloma and breast cancer patients. When comparing treatment with chemotherapy plus IV bisphosphonates to chemotherapy alone, patients receiving bisphosphonates were less likely to experience complications related to cancerous involvement of the bone such as fractures. Additionally, patients receiving bisphosphonates lived longer, had a lesser need for radiation and surgical treatment, and experienced significantly less pain than those patients not receiving bisphosphonates

Zometa® demonstrates the strongest activity of these two bisphosphonate drugs. In a recent clinical trial, Zometa® was shown to be a safe and effective treatment in prostate cancer patients with bone metastases. Compared to placebo, Zometa® significantly reduced the proportion of patients who experienced skeletal complications, extended the time to first skeletal complication, and significantly reduced the risk of skeletal complications over the course of this 15-month study. These results are notable because they show activity of Zometa® in blastic lesions, in which extra bone has built up, whereas previous trials have only shown activity of bisphosphonates on metastases in which the bone is weakened.

Another benefit of Zometa® is that it is administered in a dose ten times lower than Aredia®. This considerably reduces administration time from several hours to 15 minutes, resulting in a more convenient regimen for patients.