The Use of Zoledronic Acid in Men Receiving Androgen Deprivation Therapy for Prostate Cancer With Severe Osteopenia or Osteoporosis
Objectives
To study the effect of zoledronic acid on patients with pre-existing osteoporosis on androgen deprivation therapy (ADT), who are at highest risk for fracture. Zoledronic acid is a potent bisphosphonate that can prevent osteoporosis in patients with nonmetastatic (M0), prostate cancer (CaP) who are initiating ADT. The effect of zoledronic acid on patients with pre-existing osteoporosis on ADT, who are highest risk for fracture, has not been adequately studied.
Methods
We enrolled 28 patients with M0 CaP on ADT with severe osteopenia or osteoporosis (baseline bone-mineral density (BMD) T score < −2.0) in this open-label, single-arm trial to assess the effect of zoledronic acid on BMD. All patients also received supplemental calcium and vitamin D, and were counseled about lifestyle modifications. Patients received zoledronic acid (4 mg) intravenously every 3 months for 4 treatments. BMD was measured by dual energy X-ray absorptiometry scan at enrollment, 6 and 12 months. Primary endpoint was percent change in lumbar spine BMD.
Results
This was a high-risk patient population—primarily older Caucasians (mean age, 73 years), former smokers, and moderate users of alcohol. Mean duration of ADT was 2.4 years. Pre-existing osteopenia or osteoporosis was observed in a single site in 9 patients and multiple sites in 19 (68%). After 12 months of zoledronic acid, lumbar spine BMD increased 4.17% (P < .0001), and BMD increased significantly (P < .05) in both hips and the right femoral neck. Seven patients (25%) experienced improved BMD into the nonosteoporotic range (T score > −2.0). Zoledronic acid infusion was well tolerated and without substantial renal toxicity.
Conclusions
Zoledronic acid improves BMD in men with M0 CaP on ADT with severe osteopenia or osteoporosis (T scores < 2.0). This novel finding identifies a high-risk patient population that can potentially benefit from bisphosphonate therapy.
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This investigator-initiated study was supported by a grant from Novartis Pharmaceutical Corporation, East Hanover, NJ.
The protocol design, study conduct, results review, statistical analysis, and protocol monitoring were conducted independently by the Cooperative Studies Coordinating Center, Hines, IL. The study medication was provided by Novartis Pharmaceuticals Corporation and distributed by the Cooperative Studies Clinical Research Pharmacy Coordinating Center, Albuquerque, NM.
Organizational members of the Zoledronic Acid Trial (The use of zoledronic acid in men on androgen deprivation therapy for prostate cancer with preexisting osteoporosis”) were as follows: Principal investigators (Grant and Protocol development), Steven C. Campbell and Nirmala Bhoopalam; Co-Principal investigator (Grant and Protocol development), H. Garewal; Site Investigators, Steven C. Campbell and N. Bhoopalam (Hines, IL.), P. VanVeldhuizen (Kansas City, MO), P. Iyer (Long Beach, CA), A. Arcenas (Washington, DC), C. Vera (Boston, MA), H Gareval (Tucson, AZ); Cooperative Studies Coordinating Center, Hines, IL (Design, management, monitoring, and analysis of the study), Domenic J. Reda, Thomas E. Moritz, Nancy K. Ellis, Lizy Thottapurathu, Mazen Abdellatif, Jan Motyka; DXA central review, Nicholas Friedman (Hines, IL); Cooperative Studies Clinical Research Pharmacy Coordinating Center (Albuquerque, NM) (distribution of study drug and placebo), Stuart Warren, Jolene Day; Clinical Coordinator, Regina Chorley (Hines, IL.); Site Coordinators, I. Makar (Hines, IL), K. Gomes (Kansas City, MO), C. Kaneshiro (Long Beach, CA); Executive Committee, N. Bhoopalam (Chair), S. Campbell, H. Garewal, N. Friedman, M. Terris, D. J. Reda, S. Warren, T. E. Moritz, R. Chorley, N. K. Ellis, L. Lacerna (Novartis representation); Data Monitoring Board, R. Adler (Chair), M. Gong, G. McCabe, M. Spaulding.
Participating VA hospitals: Hines VA Medical center, Hines, IL; VA Long Beach Health Care System, Long Beach, CA; Kansas City VA, Kansas City, MO; Southern Arizona VA Health Care System, Tucson, AZ; Washington, DC VA Medical Center, Washington, DC; VA Boston Healthcare System, Jamaica Plain Division, Boston, MA.
PII: S0090-4295(10)00045-2
doi:10.1016/j.urology.2009.11.083
© 2010 Elsevier Inc. All rights reserved.
