© 2002 by Oxford University Press
Journal of the National Cancer Institute, Vol. 94, No. 19, 1458-1468,
October 2, 2002
© 2002 Oxford University Press
ARTICLE |
A Randomized, Placebo-Controlled Trial of Zoledronic Acid in Patients With Hormone-Refractory Metastatic Prostate Carcinoma
For the Zoledronic Acid Prostate Cancer Study Group
Affiliations of authors: F. Saad, Centre Hospitalier de l'Université de Montréal, Hôpital Notre-Dame, Montréal, Quebec, Canada; D. M. Gleason, Advanced Clinical Therapeutics, Tucson, AZ; R. Murray, Division of Hematology and Medical Oncology, Peter MacCallum Cancer Institute, East Melbourne, Victoria, Australia; S. Tchekmedyian, Pacific Shores Medical Group, Long Beach, CA; P. Venner, Cross Cancer Center, Edmonton, Alberta, Canada; L. Lacombe, CHUQ-Hôtel-Dieu de Quebec, Quebec, Quebec, Canada; J. L. Chin, London Health Sciences Centre, London, Ontario, Canada; J. J. Vinholes, Irmandade de Santa Casa de Misericordia de Porto Alegre, Rio Grande do Sul, Brazil; J. A. Goas, B. Chen, Novartis Pharmaceuticals Corporation, East Hanover, NJ.
Correspondence to: Fred Saad, M.D., Uro-Oncology Clinic, Centre Hospitalier de l'Université de Montréal, Hôpital Notre-Dame, 1560 Rue Sherbrooke East, Montréal, Quebec, Canada H2L 4M1 (e-mail: fred.saad{at}ssss.gouv.qc.ca).
Background: Bone metastases are a common cause of morbidity in patients with prostate carcinoma. We studied the effect of a new bisphosphonate, zoledronic acid, which blocks bone destruction, on skeletal complications in prostate cancer patients with bone metastases. Methods: Patients with hormone-refractory prostate cancer and a history of bone metastases were randomly assigned to a double-blind treatment regimen of intravenous zoledronic acid at 4 mg (N = 214), zoledronic acid at 8 mg (subsequently reduced to 4 mg; 8/4) (N = 221), or placebo (N = 208) every 3 weeks for 15 months. Proportions of patients with skeletal-related events, time to the first skeletal-related event, skeletal morbidity rate, pain and analgesic scores, disease progression, and safety were assessed. All statistical tests were two-sided. Results: Approximately 38% of patients who received zoledronic acid at 4 mg, 28% who received zoledronic acid at 8/4 mg, and 31% who received placebo completed the study. A greater proportion of patients who received placebo had skeletal-related events than those who received zoledronic acid at 4 mg (44.2% versus 33.2%; difference = –11.0%, 95% confidence interval [CI] = –20.3% to –1.8%; P = .021) or those who received zoledronic acid at 8/4 mg (38.5%; difference versus placebo = –5.8%, 95% CI = –15.1% to 3.6%; P = .222). Median time to first skeletal-related event was 321 days for patients who received placebo, was not reached for patients who received zoledronic acid at 4 mg (P = .011 versus placebo), and was 363 days for those who received zoledronic acid at 8/4 mg (P = .491 versus placebo). Compared with urinary markers in patients who received placebo, urinary markers of bone resorption were statistically significantly decreased in patients who received zoledronic acid at either dose (P = .001). Pain and analgesic scores increased more in patients who received placebo than in patients who received zoledronic acid, but there were no differences in disease progression, performance status, or quality-of-life scores among the groups. Zoledronic acid at 4 mg given as a 15-minute infusion was well tolerated, but the 8-mg dose was associated with renal function deterioration. Conclusion: Zoledronic acid at 4 mg reduced skeletal-related events in prostate cancer patients with bone metastases.
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Correspondence about this Article
- Re: A Randomized, Placebo-Controlled Trial of Zoledronic Acid in Patients With Hormone-Refractory Metastatic Prostate Carcinoma
- Eric Winquist and Scott Berry
J Natl Cancer Inst 2004 96: 1183.[Extract] [Full Text] [PDF]
- RESPONSE: Re: A Randomized, Placebo-Controlled Trial of Zoledronic Acid in Patients With Hormone-Refractory Metastatic Prostate Carcinoma
- Fred Saad
J Natl Cancer Inst 2004 96: 1183-1184.[Extract] [Full Text] [PDF]
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