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The role of bisphosphonates in hormone-refractory prostate cancer

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Abstract

Men with advanced prostate cancer are at high risk for developing bone metastases, which result in clinically significant skeletal morbidity. Treatments that prevent skeletal complications in these patients could considerably improve their quality of life. Therefore, this paper reviews the role of bisphosphonates in the treatment of hormone-refractory prostate cancer (HRPC). Published studies were identified through MEDLINE searches, review of bibliographies of relevant articles, and review of abstracts from scientific meetings. Metastatic bone disease in men with HRPC results in skeletal complications such as pathologic fractures, spinal cord compression, and debilitating bone pain. First- and second-generation bisphosphonates, clodronate and pamidronate, had transient palliative effects that were not durable and did not prevent skeletal events in these patients. A small open-label study of ibandronate demonstrated significant reductions in pain, but these results have not been confirmed in a larger, randomized, controlled trial. To date, zoledronic acid is the only bisphosphonate that has demonstrated a statistically significant reduction in skeletal morbidity in this patient population. In a large, multicenter, randomized, placebo-controlled trial, treatment of men with HRPC and bone metastases with zoledronic acid significantly reduced skeletal-related events and provided a durable reduction of bone pain over 24 months compared with placebo. Zoledronic acid is the only bisphosphonate that has demonstrated efficacy for preventing skeletal complications in patients with HRPC and bone metastases. Therefore, initiation of zoledronic acid therapy should be considered to prevent skeletal morbidity and improve the quality of life of these patients.

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References

  1. Parkin DM, Pisani P, Ferlay J (1999) Global cancer statistics. CA Cancer J Clin 49:33–64

    CAS  PubMed  Google Scholar 

  2. Ferlay J, Bray F, Pisani P, Parkin DM (2001) GLOBOCAN 2000: cancer incidence, mortality and prevalence worldwide, version 1.0. IARC CancerBase No. 5. IARC, Lyon. Accessed 21 June 2004

    Google Scholar 

  3. Hussain SA, Weston R, Stephenson RN, George E, Parr NJ (2003) Immediate dual energy x-ray absorptiometry reveals a high incidence of osteoporosis in patients with advanced prostate cancer before hormonal manipulation. BJU Int 92:690–694

    Article  Google Scholar 

  4. Pfeilschifter J, Diel IJ (2000) Osteoporosis due to cancer treatment: pathogenesis and management. J Clin Oncol 18:1570–1593

    Google Scholar 

  5. Carlin BI, Andriole GL (2000) The natural history, skeletal complications, and management of bone metastases in patients with prostate carcinoma. Cancer 88 [Suppl]:2989–2994

    Google Scholar 

  6. Coleman RE (2001) Metastatic bone disease: clinical features, pathophysiology and treatment strategies. Cancer Treat Rev 27:165–176

    Article  CAS  PubMed  Google Scholar 

  7. Coleman RE (1997) Skeletal complications of malignancy. Cancer 80 [Suppl]:1588–1594

    Google Scholar 

  8. Saad F, Gleason DM, Murray R et al. (2004) Long-term efficacy of zoledronic acid for the prevention of skeletal complications in patients with metastatic hormone-refractory prostate cancer. J Natl Cancer Inst 96:879–882

    Google Scholar 

  9. Weinfurt KP, Li Y, Castel LD, Timbie JW, Glendenning A, Schulman KA (2002) The impact of skeletal-related events on health-related quality of life of patients with metastatic prostate cancer. Ann Oncol 13 [Suppl 5]:180

    Google Scholar 

  10. Oefelein MG, Ricchiuti V, Conrad W, Resnick MI (2002) Skeletal fractures negatively correlate with overall survival in men with prostate cancer. J Urol 168:1005–1007

    Article  Google Scholar 

  11. Lipton A (2003) Management of metastatic bone disease and hypercalcemia of malignancy. Am J Cancer 2:427–438

    Google Scholar 

  12. Carey PO, Lippert MC (1988) Treatment of painful prostatic bone metastases with oral etidronate disodium. Urology 32:403–407

    Article  Google Scholar 

  13. Kylmala T, Tammela TL, Lindholm TS, Seppanen J (1994) The effect of combined intravenous and oral clodronate treatment on bone pain in patients with metastatic prostate cancer. Ann Chir Gynaecol 83:316–319

    Google Scholar 

  14. Cresswell SM, English PJ, Hall RR, Roberts JT, Marsh MM (1995) Pain relief and quality-of-life assessment following intravenous and oral clodronate in hormone-escaped metastatic prostate cancer. Br J Urol 76:360–365

    Google Scholar 

  15. Heidenreich A, Hofmann R, Engelmann UH (2001) The use of bisphosphonate for the palliative treatment of painful bone metastasis due to hormone refractory prostate cancer. J Urol 165:136–140

    Article  CAS  PubMed  Google Scholar 

  16. Lipton A, Glover D, Harvey H et al. (1994) Pamidronate in the treatment of bone metastases: results of 2 dose-ranging trials in patients with breast or prostate cancer. Ann Oncol 5 [Suppl 7]:S31-S35

  17. Heidenreich A, Elert A, Hofmann R (2002) Ibandronate in the treatment of prostate cancer associated painful osseous metastases. Prostate Cancer Prostatic Dis 5:231–235

    Article  Google Scholar 

  18. Elomaa I, Kylmälä T, Tammela T et al. (1992) Effect of oral clodronate on bone pain. A controlled study in patients with metastatic prostatic cancer. Int Urol Nephrol 24:159–166

    Google Scholar 

  19. Kylmälä T, Taube T, Tammela TLJ, Risteli L, Risteli J, Elomaa I (1997) Concomitant i.v. and oral clodronate in the relief of bone pain—a double-blind placebo-controlled study in patients with prostate cancer. Br J Cancer 76:939–942

    Google Scholar 

  20. Strang P, Nilsson S, Brandstedt S et al. (1997) The analgesic efficacy of clodronate compared with placebo in patients with painful bone metastases from prostatic cancer. Anticancer Res 17:4717–4721

    Google Scholar 

  21. Ernst DS, Tannock IF, Winquist EW et al. (2003) Randomized, double-blind, controlled trial of mitoxantrone/prednisone and clodronate versus mitoxantrone/prednisone and placebo in patients with hormone-refractory prostate cancer and pain. J Clin Oncol 21:3335–3342

    Google Scholar 

  22. Small EJ, Smith MR, Seaman JJ, Petrone S, Kowalski MO (2003) Combined analysis of two multicenter, randomized, placebo-controlled studies of pamidronate disodium for the palliation of bone pain in men with metastatic prostate cancer. J Clin Oncol 21:4277–4284

    Google Scholar 

  23. Saad F, Gleason D, Murray R et al. (2003) Zoledronic acid is well tolerated for up to 24 months and significantly reduces skeletal complications in patients with advanced prostate cancer metastatic to bone. American Urological Association Annual Meeting, April 26–May 1 2003, Chicago, Illinois. Abstract 1472

  24. Lipton A, Small E, Saad F et al. (2002) The new bisphosphonate, Zometa (zoledronic acid), decreases skeletal complications in both osteolytic and osteoblastic lesions: a comparison to pamidronate. Cancer Invest 20 [Suppl 2]:45–54

    Google Scholar 

  25. Saad F, Gleason D, Murray R et al. (2003) Long-term reduction of bone pain with zoledronic acid in patients with advanced prostate cancer metastatic to bone. American Urological Association Annual Meeting, April 26–May 1 2003, Chicago, Illinois. Abstract 1473

  26. Carroll PR, Altwein J, Brawley O et al. (2003) Management of disseminated prostate cancer. In: Denis L, Bartsch G, Khoury S et al. (eds) Prostate cancer: Third International Consultation on Prostate Cancer, Paris. Health Publications, Paris, pp 249–284

  27. Smith MR, Eastham J, Gleason DM, Shasha D, Tchekmedyian S, Zinner N (2003) Randomized controlled trial of zoledronic acid to prevent bone loss in men receiving androgen deprivation therapy for nonmetastatic prostate cancer. J Urol 169:2008–2012

    CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Division of Urology, Department of Surgery, Centre Hospitalier de l’Université de Montréal, Montréal, PQ H2L 4M1 Quebec, 1560 Rue Sherbrooke East, Canada

    Fred Saad, Pierre Karakiewicz & Paul Perrotte

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  1. Fred Saad
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  2. Pierre Karakiewicz
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  3. Paul Perrotte
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Correspondence to Fred Saad.

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Saad, F., Karakiewicz, P. & Perrotte, P. The role of bisphosphonates in hormone-refractory prostate cancer. World J Urol 23, 14–18 (2005). https://doi.org/10.1007/s00345-004-0472-2

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  • DOI: https://doi.org/10.1007/s00345-004-0472-2

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