Open Access

ARTICLE

The use of bisphosphonates in men with hormonerefractory prostate cancer: a systematic review of randomized trials

Scott Berry¹, Tricia Waldron², Eric Winquist³, Himu Lukka⁴, on behalf of the Cancer Care Ontario Program in Evidence-based Care’s Genitourinary Cancer Disease Site Group⁵

1 Toronto-Sunnybrook Regional Cancer Centre, Toronto, Ontario, Canada
2 Cancer Care Ontario Program in Evidence-based Care, McMaster University, Hamilton, Ontario, Canada
3 London Health Sciences Centre, London, Ontario, Canada
4 Juravinski Cancer Centre, Hamilton, Ontario, Canada
5 http://www.cancercare.on.ca/index_genitourinaryCancerdsg.htm.
Address correspondence to Ms. Tricia Waldron, Cancer Care Ontario Program in Evidence-based Care, McMaster University, DTC, 3^rd Floor, Room 315, 1280 Main Street West, Hamilton, Ontario L8S 4L8 Canada

Canadian Journal of Urology 2006, 13(4), 3180-3188.

Abstract

Purpose: A systematic review of randomized controlled trials (RCTs) was performed to assess the benefits of bisphosphonate therapy in men with hormone-refractory prostate cancer (HRPC).
Methods: The literature was searched to identify RCTs or meta-analyses comparing treatment with bisphosphonates to placebo or no treatment.
Results: Ten trials that studied clodronate (five trials, 404 patients), pamidronate (two trials, 350 patients), alendronate (one trial, 49 patients), etidronate (one trial, 51 patients), and zoledronic acid (one trial, 643 patients) in men with HRPC and bone metastases met the eligibility criteria. Pain response was the most frequently reported primary outcome (eight trials). Only the smallest trial demonstrated a statistically significant improvement in pain, but other non-statistically significant trends and subgroup analyses showing improvement in pain were observed in six clodronate and pamidronate trials. Three trials reported skeletal-related events (SREs). A trial studying zoledronic acid reported a statistically and clinically significant reduction in the number of patients having at least one SRE; however, there were higher rates of some adverse effects, and quality of life was not improved.
Conclusion: Zoledronic acid appears to reduce the number of patients having at least one SRE in men with bone metastases from HRPC that are causing minimal or no pain. This benefit should be weighed against the associated toxicities, and the neutral effect on quality of life. Bisphosphonates may reduce bone pain in men with HRPC, but the evidence is less robust. Further investigations to identify the role of bisphosphonates alone and in combination with other therapies proven effective for men with HRPC are warranted.

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