Zoledronic Acid in the Management of Metastatic Bone Disease

Overview

Journal Ther Clin Risk Manag

Publisher Dove Medical Press

Date 2008 Aug 30

PMID 18728715

Citations 33

Authors

Thomas J Polascik

Vladimir Mouraviev

Affiliations

Soon will be listed here.

Abstract

Many patients with advanced cancer experience decreased bone strength due to metastatic foci, underlying osteoporosis and/or cancer treatment induced bone loss. The clinical consequences of metastatic disease involving the skeleton are widespread. This review focuses on the efficacy, pharmacology, and safety when using intravenous biphosphonate such a zoledronic acid for cancer bone metastases. Zoledronic acid is the gold standard for the medical management of metastatic bone disease. The indications for treatment include prevention of skeletal relevant events (SRE), osteoporotic complications, and palliation of bone pain, among others. Zoledronic acid is the only bisphosphonate effective in decreasing SREs associated with bone metastases from advanced renal cell carcinoma and prostate cancer. Regarding prostate cancer, zoledronic acid effectively prevents both bone loss in patients with locally advanced disease receiving androgen deprivation therapy and SREs in men with hormone-refractory or hormone-sensitive metastatic disease. Zoledronic acid has an acceptable safety profile and tolerability, and has been effective at significantly decreasing the incidence, delaying the onset, and reducing the overall risk of experiencing an SRE compared to placebo. It is the only bisphosphonate currently approved for the prevention and treatment of skeletal complications in patients with bone metastases due to all solid tumors.

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References

Smith M, Eastham J, Gleason D, Shasha D, Tchekmedyian S, Zinner N . Randomized controlled trial of zoledronic acid to prevent bone loss in men receiving androgen deprivation therapy for nonmetastatic prostate cancer. J Urol. 2003; 169(6):2008-12. DOI: 10.1097/01.ju.0000063820.94994.95. View

Wardley A, Davidson N, Barrett-Lee P, Hong A, Mansi J, Dodwell D . Zoledronic acid significantly improves pain scores and quality of life in breast cancer patients with bone metastases: a randomised, crossover study of community vs hospital bisphosphonate administration. Br J Cancer. 2005; 92(10):1869-76. PMC: 2361764. DOI: 10.1038/sj.bjc.6602551. View

Clemons M, Dranitsaris G, Ooi W, Yogendran G, Sukovic T, Wong B . Phase II trial evaluating the palliative benefit of second-line zoledronic acid in breast cancer patients with either a skeletal-related event or progressive bone metastases despite first-line bisphosphonate therapy. J Clin Oncol. 2006; 24(30):4895-900. DOI: 10.1200/JCO.2006.05.9212. View

Michaelson M, Kaufman D, Lee H, McGovern F, Kantoff P, Fallon M . Randomized controlled trial of annual zoledronic acid to prevent gonadotropin-releasing hormone agonist-induced bone loss in men with prostate cancer. J Clin Oncol. 2007; 25(9):1038-42. PMC: 3047397. DOI: 10.1200/JCO.2006.07.3361. View

Polascik T, Given R, Metzger C, Julian S, Vestal J, Karlin G . Open-label trial evaluating the safety and efficacy of zoledronic acid in preventing bone loss in patients with hormone-sensitive prostate cancer and bone metastases. Urology. 2005; 66(5):1054-9. DOI: 10.1016/j.urology.2005.05.035. View

Rosen L, Gordon D, Kaminski M, Howell A, Belch A, Mackey J . Zoledronic acid versus pamidronate in the treatment of skeletal metastases in patients with breast cancer or osteolytic lesions of multiple myeloma: a phase III, double-blind, comparative trial. Cancer J. 2001; 7(5):377-87. View

Green J, Muller K, Jaeggi K . Preclinical pharmacology of CGP 42'446, a new, potent, heterocyclic bisphosphonate compound. J Bone Miner Res. 1994; 9(5):745-51. DOI: 10.1002/jbmr.5650090521. View

Rosen L, Gordon D, Dugan Jr W, Major P, Eisenberg P, Provencher L . Zoledronic acid is superior to pamidronate for the treatment of bone metastases in breast carcinoma patients with at least one osteolytic lesion. Cancer. 2003; 100(1):36-43. DOI: 10.1002/cncr.11892. View

Cummings S, Bates D, Black D . Clinical use of bone densitometry: scientific review. JAMA. 2002; 288(15):1889-97. DOI: 10.1001/jama.288.15.1889. View

10.

Boissier S, Ferreras M, Peyruchaud O, Magnetto S, Ebetino F, Colombel M . Bisphosphonates inhibit breast and prostate carcinoma cell invasion, an early event in the formation of bone metastases. Cancer Res. 2000; 60(11):2949-54. View

11.

Flanigan R, Campbell S, Clark J, Picken M . Metastatic renal cell carcinoma. Curr Treat Options Oncol. 2003; 4(5):385-90. DOI: 10.1007/s11864-003-0039-2. View

12.

Saad F, Gleason D, Murray R, Tchekmedyian S, Venner P, Lacombe L . A randomized, placebo-controlled trial of zoledronic acid in patients with hormone-refractory metastatic prostate carcinoma. J Natl Cancer Inst. 2002; 94(19):1458-68. DOI: 10.1093/jnci/94.19.1458. View

13.

Kohno N, Aogi K, Minami H, Nakamura S, Asaga T, Iino Y . Zoledronic acid significantly reduces skeletal complications compared with placebo in Japanese women with bone metastases from breast cancer: a randomized, placebo-controlled trial. J Clin Oncol. 2005; 23(15):3314-21. DOI: 10.1200/JCO.2005.05.116. View

14.

Garnero P, Buchs N, Zekri J, Rizzoli R, Coleman R, Delmas P . Markers of bone turnover for the management of patients with bone metastases from prostate cancer. Br J Cancer. 2000; 82(4):858-64. PMC: 2374389. DOI: 10.1054/bjoc.1999.1012. View

15.

Oefelein M, Ricchiuti V, Conrad W, Resnick M . Skeletal fractures negatively correlate with overall survival in men with prostate cancer. J Urol. 2002; 168(3):1005-7. DOI: 10.1016/S0022-5347(05)64561-2. View

16.

Martel C, Lara P . Renal cell carcinoma: current status and future directions. Crit Rev Oncol Hematol. 2003; 45(2):177-90. DOI: 10.1016/s1040-8428(02)00076-8. View

17.

Smith M, Boyce S, Moyneur E, Duh M, Raut M, Brandman J . Risk of clinical fractures after gonadotropin-releasing hormone agonist therapy for prostate cancer. J Urol. 2006; 175(1):136-9. DOI: 10.1016/S0022-5347(05)00033-9. View

18.

Zekri J, Ahmed N, Coleman R, Hancock B . The skeletal metastatic complications of renal cell carcinoma. Int J Oncol. 2001; 19(2):379-82. DOI: 10.3892/ijo.19.2.379. View

19.

Lipton A . Pathophysiology of bone metastases: how this knowledge may lead to therapeutic intervention. J Support Oncol. 2004; 2(3):205-13. View

20.

Smith M, Lee W, Brandman J, Wang Q, Botteman M, Pashos C . Gonadotropin-releasing hormone agonists and fracture risk: a claims-based cohort study of men with nonmetastatic prostate cancer. J Clin Oncol. 2005; 23(31):7897-903. DOI: 10.1200/JCO.2004.00.6908. View