In men with three or fewer bone metastases at enrollment, zoledronic acid cut overall risk by 37%.


PARIS—Zoledronic acid reduces the risk of a first skeletal-related event (SREs) in patients with early malignant bone disease associated with hormone-refractory prostate cancer (HRPC).

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The finding comes from an analysis of a subset of phase III trial participants who had not yet experienced an SRE. In a previous analysis of data from the phase III, zoledronic acid significantly delayed onset of SREs in patients with HRPC who already had suffered at least one SRE.


The researchers, led by Fred Saad, MD, director of urologic oncology at the University of Montreal, reasoned that earlier treatment of bone metastases, before onset of SREs, “may have a more profound effect on clinical outcomes and quality of life.”


In the new study, presented here at the Société Internationale d’Urologie 29th Congress, investigators assigned patients to receive either a placebo (130 patients) or a 15-minute infusion of 4 mg of zoledronic acid (147 patients) every three weeks in addition to standard HRPC therapy. They were then evaluated for the occurrence of SREs, specifically pathologic fracture, spinal cord compression, rardiation therapy to bone or bone surgery, or change in antineoplastic therapy to treat bone pain. 


Dr. Saad and his colleagues found that zoledronic acid did have beneficial effects in patients in

earlier stages of bone metastases. The median time to first SRE in the placebo group was 337 days compared with 499 days in the zoledronic acid group, a difference of approximately six months, the investigators reported.


In patients with three or fewer bone metastases prior to study enrollment, zoledronic acid reduced the overall risk of an SRE by 37% compared with placebo recipients, the study showed.


In addition, zoledronic acid treatment led to an 85% decrease in the skeletal morbidity rate, or number of SREs per year, in patients with only one bone metastasis prior to the start of the study. This subset of patients, however, was small (23 patients in the zoledronic acid group and 28 in the placebo group), so the difference was not statistically significant, the researchers noted.


In another study by Dr. Saad and colleagues, elevated bone markers were a common finding in patients wtih metastatic prostate cancer. Patients who had normalization of these markers had a significantly better outcome and survival than those who did not have normalization.


“This study demonstrates that the bone marker normalization at three months has significant predictive outcome,” Dr. Saad said. “This leads us to believe that bone markers should play a bigger role in the clinic and may help in making decisions in patients with bone mets.”