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Osteoclast-targeted therapy for prostate cancer

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Opinion statement

Skeletal complications are a major cause of morbidity in men with metastatic prostate cancer. Bone metastases cause pain, fractures, spinal-cord compression, and ineffec-tive hematopoiesis. Men without bone metastases are also at risk for skeletal complications. Androgen deprivation therapy (ADT), the mainstay of treatment for metastatic prostate cancer and a routine part of the management for many men with nonmetastatic prostate cancer, decreases bone mineral density, and increases fracture risk. Pathological osteoclast activation plays a central role in both disease and treatment-related skeletal morbidity. Bisphosphonates, potent inhibitors of osteoclast activity, are now an important part of the management for many men with prostate cancer. Zoledronic acid, a potent intravenous bisphosphonate, decreases the risk of skeletal complications in men with hormone-refractory prostate cancer and bone metastases. Zoledronic acid and pamidronate preserve bone mineral density in men receiving ADT for nonmetastatic prostate cancer. Ongoing clinical trials will evaluate the role of osteoclast-targeted therapy in other settings including prevention of treatment-related fractures, prevention of bone metastases in men with high-risk nonmetastatic prostate cancer, and prevention of skeletal complications in men with hormone-sensi-tive metastatic disease.

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References and Recommended Reading

  1. Harada M, Iida M, Yamaguchi M, Shida K: Analysis of bone metastasis of prostatic adenocarcinoma in 137 autopsy cases. Adv Exp Med Biol 1992, 324:173–182.

    PubMed  CAS  Google Scholar 

  2. Clarke NW, McClure J, George NJ: Osteoblast function and osteomalacia in metastatic prostate cancer. Eur Urol 1993, 24:286–290.

    PubMed  CAS  Google Scholar 

  3. Clarke NW, McClure J, George NJ: Morphometric evi-dence for bone resorption and replacement in pros-tate cancer. Br J Urol 1991, 68:74–80.

    Article  PubMed  CAS  Google Scholar 

  4. Garnero P, Sornay-Rendu E, Claustrat B, Delmas PD: Biochemical markers of bone turnover, endogenous hormones and the risk of fractures in postmeno-pausal women: the OFELY study. J Bone Miner Res 2000, 15:1526–1536.

    Article  PubMed  CAS  Google Scholar 

  5. Berruti A, Dogliotti L, Bitossi R, et al.: Incidence of skel-etal complications in patients with bone metastatic prostate cancer and hormone refractory disease: pre-dictive role of bone resorption and formation mark-ers evaluated at baseline. J Urol 2000, 164:1248–1253.

    Article  PubMed  CAS  Google Scholar 

  6. Murray RM, Grill V, Crinis N, et al.: Hypocalcemic and normocalcemic hyperparathyroidism in patients with advanced prostatic cancer. J Clin Endocrinol Metab 2001, 86:4133–4138.

    Article  PubMed  CAS  Google Scholar 

  7. Smith MR, McGovern FJ, Zietman AL, et al.: Pamidr-onate to prevent bone loss in men receiving gonadot-ropin releasing hormone agonist therapy for prostate cancer. N Engl J Med 2001, 345:948–955.

    Article  PubMed  CAS  Google Scholar 

  8. Higano CS: Management of bone loss in men with pros-tate cancer. J Urol 2003, 170:S59-S63;discussion S64.

    Article  PubMed  Google Scholar 

  9. Rogers MJ, Watts DJ, Russell RG: Overview of bisphos-phonates. Cancer 1997, 80:1652–1660.

    Article  PubMed  CAS  Google Scholar 

  10. Rosen LS, Gordon D, Kaminski M, et al.: 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, 7:377 -387.

    PubMed  CAS  Google Scholar 

  11. Rosen LS, Gordon D, Tchekmedyian S, et al.: Zoledronic acid versus placebo in the treatment of skeletal metastases in patients with lung cancer and other solid tumors: a phase III, double-blind, randomized trial--the Zoledronic Acid Lung Cancer and Other Solid Tumors Study Group. J Clin Oncol 2003, 21:3150–3157.

    Article  PubMed  CAS  Google Scholar 

  12. Saad F, Gleason DM, Murray R, et al.: A randomized, placebo-controlled trial of zoledronic acid in patients with hormone-refractory metastatic prostate carci-noma. J Natl Cancer Inst 2002, 94:1458 -1468. This pivotal randomized controlled trial demonstrated that zoledronic acid decreases risk of skeletal complications in men with hormone-refractory prostate cancer and bone metastases. It provides the first proof of principle for osteo-clast- targeted therapy in men with metastatic prostate cancer and established a new standard for treatment.

    PubMed  CAS  Google Scholar 

  13. Small EJ, Smith MR, Seaman JJ, et al.: Combined analy-sis of two multicenter, randomized, placebo-con-trolled studies of pamidronate disodium for the palliation of bone pain in men with metastatic pros-tate cancer. J Clin Oncol 2003, 21:4277–4284.

    Article  PubMed  CAS  Google Scholar 

  14. Ernst D, Tannock I, Venner P, et al.: Randomized pla-cebo controlled trial of mitoxantrone/prednisone and clodronate versus mitoxantrone/prednisone alone in patients with hormone refractory prostate cancer (HRPC) and pain: National Cancer Institute of Can-ada Clinical Trials Group study. Proc Am Soc Clin Oncol 2002, Abstract 705:177a.

  15. Dearnaley DP, Sydes MR, Mason MD, et al.: A double-blind, placebo-controlled, randomized trial of oral sodium clodronate for metastatic prostate cancer (MRC PR05 Trial). J Natl Cancer Inst 2003, 95:1300–1311. This randomized controlled trial evaluated the efficacy of clo-dronate in men with hormone-sensitive metastatic prostate cancer. Bone progression-free survival and overall survival did not differ significantly between the groups, but the trend toward better outcomes sets the stage for CALGB 90202—a larger study of zoledronic acid in similar patient population.

    PubMed  CAS  Google Scholar 

  16. Mason MD, Collaborators MP: Development of bone metastases from prostate cancer: first results of the MRC PR04 trial (ISCRTN 61384873) [abstract]. Proc Am Soc Clin Oncol 2004, 4511.

  17. Diamond TH, Winters J, Smith A, et al.: The antios-teoporotic efficacy of intravenous pamidronate in men with prostate carcinoma receiving combined androgen blockade: a double blind, randomized, pla-cebo- controlled crossover study. Cancer 2001, 92:1444–1450.

    Article  PubMed  CAS  Google Scholar 

  18. Smith MR, Eastham J, Gleason D, et al.: Randomized controlled trial of zoledronic acid to prevent bone loss in men undergoing ADT for nonmetastatic pros-tate cancer. J Urol 2003, 169:2008–2012. This multicentered randomized controlled trial demonstrated that zoledronic acid increases bone mineral density in men receiving ADT. The results of this study make zoledronic acid an attractive option to prevent treatment-related osteoporosis.

    Article  PubMed  CAS  Google Scholar 

  19. Smith MR, McGovern FJ, Fallon MA, et al.: Low bone mineral density in hormone-naive men with prostate carcinoma. Cancer 2001, 91:2238–2245.

    Article  PubMed  CAS  Google Scholar 

  20. Bilezikian JP: Osteoporosis in men. J Clin Endocrinol Metab 1999, 84:3431–3434.

    Article  PubMed  CAS  Google Scholar 

  21. Dawson-Hughes B, Harris SS, Krall EA, Dallal GE: Effect of calcium and vitamin D supplementation on bone density in men and women 65 years of age or older. N Engl J Med 1997, 337:670–676.

    Article  PubMed  CAS  Google Scholar 

  22. Giovannucci E, Rimm EB, Wolk A, et al.: Calcium and fructose intake in relation to risk of prostate cancer. Cancer Res 1998, 58:442–447.

    PubMed  CAS  Google Scholar 

  23. Chan JM, Giovannucci E, Andersson SO, et al.: Dairy products, calcium, phosphorous, vitamin D, and risk of prostate cancer (Sweden). Cancer Causes Control 1998, 9:559–566.

    Article  PubMed  CAS  Google Scholar 

  24. Giovannucci E: Dietary influences of 1,25(OH)2 vita-min D in relation to prostate cancer: a hypothesis. Cancer Causes Control 1998, 9:567–582.

    Article  PubMed  CAS  Google Scholar 

  25. Boyle WJ, Simonet WS, Lacey DL: Osteoclast differenti-ation and activation. Nature 2003, 423:337–342.

    Article  PubMed  CAS  Google Scholar 

  26. Bekker PJ, Holloway DL, Rasmussen AS, et al.: A single-dose placebo-controlled study of AMG 162, a fully human monoclonal antibody to RANKL, in postmeno-pausal women. J Bone Miner Res 2004, 19:1059–1066.

    Article  PubMed  CAS  Google Scholar 

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  1. Massachusetts General Hospital, Cox 640, 100 Blossom Street, 02114, Boston, MA, USA

    Matthew R. Smith MD, PhD

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  1. Matthew R. Smith MD, PhD
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Smith, M.R. Osteoclast-targeted therapy for prostate cancer. Curr. Treat. Options in Oncol. 5, 367–375 (2004). https://doi.org/10.1007/s11864-004-0027-1

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  • DOI: https://doi.org/10.1007/s11864-004-0027-1

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