The Journal of Urology
Volume 182, Issue 2 , Pages 509-516 , August 2009

Denosumab Treatment of Prostate Cancer With Bone Metastases and Increased Urine N-Telopeptide Levels After Therapy With Intravenous Bisphosphonates: Results of a Randomized Phase II Trial

  • Karim Fizazi

      Affiliations

    • Institut Gustave Roussy and University of Paris XI, Villejuif, France
    • Corresponding Author InformationCorrespondence: Department of Medicine, Institut Gustave Roussy and University of Paris XI, 39 Rue Camille Desmoulins, 94800 Villejuif, France (telephone: 33 1 42 11 43 17; FAX: 33 1 42 11 52 11)
    • Financial interest and/or other relationship with Amgen, Novartis, AstraZeneca, Sanofi-Aventis, Ipsen-Beaufour, Pharmion, Bristol Myers Squibb and Takeda.
    • ,
  • Linda Bosserman

      Affiliations

    • Wilshire Oncology Medical Group, La Verne, California
    • Financial interest and/or other relationship with Amgen and Pfizer.
    • ,
  • Guozhi Gao

      Affiliations

    • Amgen Inc., San Francisco, California
    • Financial interest and/or other relationship with Amgen.
    • ,
  • Tomas Skacel

      Affiliations

    • Amgen (Europe) GmbH, Zug, Switzerland
    • Financial interest and/or other relationship with Amgen.
    • ,
  • Richard Markus

      Affiliations

    • Amgen Inc., Thousand Oaks, California
    • Financial interest and/or other relationship with Amgen.

Received 22 December 2008

References 

  1. World Health Organization. Health statistics and health information systems: Revised Global Burden of Disease (GBD) 2002 estimates. http://www.who.int/healthinfo/bodgbd2002revised/en/index.htmlAccessed May 15, 2008
  2. Coleman RE. Skeletal complications of malignancy. Cancer. 1997;80:1588
  3. Brown JE, Cook RJ, Major P, et al. Bone turnover markers as predictors of skeletal complications in prostate cancer, lung cancer, and other solid tumors. J Natl Cancer Inst. 2005;97:59
  4. Lacey DL, Tan HL, Lu J, et al. Osteoprotegerin ligand modulates murine osteoclast survival in vitro and in vivo. Am J Pathol. 2000;157:435
  5. Fizazi K, Yang J, Peleg S, et al. Prostate cancer cells-osteoblast interaction shifts expression of growth/survival-related genes in prostate cancer and reduces expression of osteoprotegerin in osteoblasts. Clin Cancer Res. 2003;9:2587
  6. Ross AB, Bateman TA, Kostenuik PJ, et al. The effects of osteoprotegerin on the mechanical properties of rat bone. J Mater Sci Mater Med. 2001;12:583
  7. Sone T, Tamada T, Jo Y, et al. Analysis of three-dimensional microarchitecture and degree of mineralization in bone metastases from prostate cancer using synchrotron microcomputed tomography. Bone. 2004;35:432
  8. Yang J, Fizazi K, Peleg S, et al. Prostate cancer cells induce osteoblast differentiation through a Cbfa1-dependent pathway. Cancer Res. 2001;61:5652
  9. Clarke NW, McClure J, George NJ. Morphometric evidence for bone resorption and replacement in prostate cancer. Br J Urol. 1991;68:74
  10. Martin RB. Skeletal biology. In:  Martin RB,  Burr DB,  Sharkey NA editor. Skeletal Tissue Mechanics. New York: Springer; 1998;p. 29–78
  11. Pfeilschifter J, Diel IJ. Osteoporosis due to cancer treatment: pathogenesis and management. J Clin Oncol. 2000;18:1570
  12. Brown JE, Thomson CS, Ellis SP, et al. Bone resorption predicts for skeletal complications in metastatic bone disease. Br J Cancer. 2003;89:2031
  13. Aapro M, Abrahamsson PA, Body JJ, et al. Guidance on the use of bisphosphonates in solid tumours: recommendations of an international expert panel. Ann Oncol. 2008;19:420
  14. Body JJ, Facon T, Coleman RE, et al. A study of the biological receptor activator of nuclear factor-kappaB ligand inhibitor, denosumab, in patients with multiple myeloma or bone metastases from breast cancer. Clin Cancer Res. 2006;12:1221
  15. Fizazi K, Lipton A, Mariette X, et al. Randomized phase II trial of denosumab in patients with bone metastases from prostate cancer, breast cancer, or other neoplasms after intravenous bisphosphonates. J Clin Oncol. 2009;27:1564
  16. Smith MR, Cook RJ, Coleman R, et al. Predictors of skeletal complications in men with hormone-refractory metastatic prostate cancer. Urology. 2007;70:315
  17. Lipton A, Steger GG, Figueroa J, et al. Extended efficacy and safety of denosumab in breast cancer patients with bone metastases not receiving prior bisphosphonate therapy. Clin Cancer Res. 2008;14:6690
  18. Fizazi K, Beuzeboc P, Lumbroso J, et al. Phase II trial of consolidation docetaxel and samarium-153 in patients with bone metastases from castration-resistant prostate cancer. J Clin Oncol. 2009;27:2429
  19. Fizazi K. The role of Src in prostate cancer. Ann Oncol. 2007;18:1765
  20. Carducci MA, Jimeno A. Targeting bone metastasis in prostate cancer with endothelin receptor antagonists. Clin Cancer Res. 2006;12:6296s

 Clinical Trial Registration NCT00104650 (www.clinicaltrials.gov).

 Supported by Amgen Inc.

 Study received institutional review board/ethics committee approval.

PII: S0022-5347(09)00932-X

doi: 10.1016/j.juro.2009.04.023

The Journal of Urology
Volume 182, Issue 2 , Pages 509-516 , August 2009

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