RESPONSE: Re: A Randomized, Placebo-Controlled Trial of Zoledronic Acid in Patients With Hormone-Refractory Metastatic Prostate Carcinoma

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Drs. Winquist and Berry stated that, because in our trial “the rate of skeletal-related events (SREs) was 44.2%” ( 1 ) , there is not adequate rationale for routine use of bisphosphonates in patients with bone metastases from advanced prostate cancer. However, we believe that the evidence supports the routine use of zoledronic acid in these patients. After 24 months of follow-up, 49% of patients in the placebo arm had experienced at least one SRE ( 2 ) , suggesting that patients with bone metastases from advanced prostate cancer are at substantial risk of skeletal complications. In fact, the risk is similar to that observed in patients with stage III multiple myeloma (51% incidence at 21 months) ( 3 ) , for which intravenous bisphosphonate therapy has been the standard of care for years. Moreover, the mean annual incidence of SREs among prostate cancer patients in the placebo arm is approximately 1.5 events per year ( 2 ) , indicating that patients often have multiple events each year. Because these patients have a median survival of 12–53 months from the time of diagnosis of bone metastases ( 4 ) , the likelihood that any given patient will experience a skeletal complication is high. More important, skeletal complications are associated with decreased quality of life ( 5 ) and survival ( 6 ) . Therefore, we believe there is sound clinical rationale for proactive treatment with zoledronic acid in patients with bone metastases from advanced prostate cancer and that the potential benefits outweigh the risks associated with bisphosphonate therapy. Adverse events associated with zoledronic acid were primarily mild-to-moderate flu-like symptoms and would not be expected to affect quality of life to the same extent as skeletal complications.