ANAHEIM, CaliforniaIn a study of advanced prostate cancer
patients, use of the investigational bisphosphonate 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
Patients receiving zoledronic acid also had a significant delay
in the time to onset of the first skeletal-related event, compared with the
"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
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
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.