Zoledronic Acid improves clinical outcomes when administered before onset of bone pain in patients with prostate cancer.
OBJECTIVE
To evaluate, in an exploratory analysis, the effect of zoledronic acid (ZOL) on skeletal-related event (SRE) incidence as determined by the bone pain levels at study entry. Bone metastases can undermine skeletal integrity long before the onset of symptoms. Treating patients before symptom onset might be more effective in preventing SREs and improving patients' quality of life. ZOL has shown significant reductions in SREs and pain compared with placebo in patients with bone metastases from advanced prostate cancer in a randomized placebo-controlled trial.


METHODS
Patients from a placebo-controlled, Phase III trial of men with castration-resistant prostate cancer, randomized to receive ZOL 4 mg (n = 214) or placebo (n = 208) for ≤ 24 months, were stratified by pain or no pain at baseline. Bone pain was assessed at baseline, week 3, and week 6 and at 6-week intervals thereafter. The primary endpoint was the proportion of patients with ≥ 1 SRE.


RESULTS
ZOL significantly reduced the mean pain scores compared with placebo at 3, 9, 21, and 24 months (P ≤ .03 for each point) and reduced the annual incidence of SREs. Among patients without baseline pain, ZOL decreased the percentage of patients with ≥ 1 SRE by 39% and reduced the annual incidence of SREs by 49% compared with placebo. ZOL delayed the onset of bone pain in those patients without pain at baseline compared with placebo.


CONCLUSIONS
ZOL reduced bone pain and SREs compared with placebo in patients with bone metastases from castration-resistant prostate cancer, irrespective of the baseline pain status, and appeared more efficacious when initiated before the onset of pain.
Centre Hospitalier de i'Université de Montréal, Hôpital Notre-Dame, Montréal, Quebec, Canada. fred.saad@umontreal.ca
Fred
F
Saad
James
J
Eastham
D000368:Aged; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000150:complications / Q000556:secondary*; D004164:Diphosphonates / Q000627:therapeutic use*; D005598:Fractures, Spontaneous / Q000150:complications; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use*; D008297:Male; D010146:Pain / Q000209:etiology / Q000517:prevention & control*; D010147:Pain Measurement; D011471:Prostatic Neoplasms / Q000401:mortality / Q000473:pathology*; D013117:Spinal Cord Compression / Q000150:complications; D015996:Survival Rate; D000077211:Zoledronic Acid
D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid