ANAHEIM, California—In a study of advanced prostate cancer patients, use of the investigational bisphosphonate zoledronic acid(Drug information on zoledronic acid) (Zometa) led to significantly fewer skeletal-related events associated with bone metastases (including radiation therapy for pain relief) than did placebo, according to data presented at the Society of Urologic Oncology meeting, held in conjunction with the 96th Annual Meeting of the American Urological Association.
Patients receiving zoledronic acid also had a significant delay in the time to onset of the first skeletal-related event, compared with the placebo group.
"Zometa represents a significant treatment advance, both in terms of its effectiveness and its infusion time, which is only 15 minutes," said principal investigator Fred Saad, MD, associate professor of urology and director of urologic oncology, Montreal Cancer Institute, University of Montreal. The agent is currently under review by the FDA for the treatment of hypercalcemia of malignancy.
In a press release, Novartis Oncology, which is developing the agent, said that this is the first time "any bisphosphonate has demonstrated efficacy in treating the bone metastases associated with prostate cancer in a well-controlled clinical trial."
Until now, the company said, bisphosphonates have been most effective in tumors where bone destruction is caused primarily by overstimulation of osteoclasts, which abnormally accelerate the breakdown of bone. In prostate cancer, bone destruction is caused primarily by osteoblasts, which overstimulate the formation of bone, leading to a defective bone infrastructure.
In this randomized, double-blind, placebo-controlled study of 422 prostate cancer patients with a history of metastatic bone disease, the treatment group received a 15-minute infusion of zoledronic acid 4 mg every 3 weeks for 15 months.
By month 15, 33% of those receiving zoledronic acid had experienced a skeletal-related event, compared with 44% of the placebo group (P = .021). The median time to first skeletal-related event was 321 days for placebo; the zoledronic acid group has not yet reached a median time to first skeletal-related event (P = .011).
Skeletal-related events included pathologic fractures, spinal cord compression/vertebral collapse, radiation therapy for pain relief, and radiation to treat or prevent pathologic fractures or spinal cord compression/collapse.
Zoledronic acid was generally well tolerated. The most common adverse effects reported in the study were bone pain, nausea, constipation, fatigue, anemia, muscle pain, vomiting, weakness, anorexia, and fever.
