Continuing benefit of zoledronic acid in preventing skeletal complications in patients with bone metastases.
OBJECTIVE
We previously reported the efficacy of zoledronic acid 4 mg versus placebo (every 3 weeks for 24 months) for the prevention of skeletal-related events (SREs) in men with advanced prostate cancer and bone metastases. We conducted several retrospective exploratory analyses to determine whether zoledronic acid has continuing efficacy during long-term treatment.


METHODS
This report included analysis of the occurrence of SREs during the extension phase only (months 16-24), analysis of skeletal complications excluding the first SRE at 15 months (core phase), and stratified analysis of patients by history of SREs before study entry.


RESULTS
Patients (N=422) were randomized to receive zoledronic acid 4 mg or placebo. For the 132 patients who entered the extension phase, zoledronic acid significantly delayed the onset of first SRE (P=.009) and decreased the risk of developing an SRE by 53% compared with placebo (P=.022). Among all 422 patients, zoledronic acid significantly reduced the incidence of a second on-study SRE (P=.017) and significantly delayed the median time to second SRE compared with placebo (P=.006) at 15 months. Among 144 patients (34%) with a history of SREs before study entry, zoledronic acid significantly reduced the skeletal morbidity rate by 65% (P=.036) and reduced the overall risk of developing an SRE by 40% (P=.028) compared with placebo at 24 months.


CONCLUSIONS
This analysis confirms our previously reported results and suggests that long-term treatment with zoledronic acid provides continuing clinical benefit in patients with advanced prostate cancer, even after the occurrence of SREs.
Saad
Fred
F
Centre Hospitalier de l'Université de Montréal, Hôpital Notre-Dame, Montréal, Quebec, Canada. fred.saad@umontreal.ca
Chen
Yin-Miao
YM
Gleason
Donald M
DM
Chin
Joseph
J
D000368:Aged; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000517:prevention & control* / Q000556:secondary; D004164:Diphosphonates / Q000627:therapeutic use*; D050723:Fractures, Bone / Q000517:prevention & control; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use*; D008297:Male; D010146:Pain / Q000517:prevention & control; D011471:Prostatic Neoplasms / Q000473:pathology*; D012189:Retrospective Studies; D000077211:Zoledronic Acid
D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid