Bone Metastases in Advanced Prostate Cancer
Bone Metastases in Advanced Prostate Cancer
US Oncology Review 2005
Published: October 2008
Published: October 2008
Abstract
Men with advanced prostate cancer are at high risk for development of bone metastases, resulting in clinically significant skeletal morbidity and severe bone pain. Studies of early-generation bisphosphonates, clodronate, and pamidronate, demonstrated transient palliative effects on bone pain in patients with bone metastases, but failed to demonstrate long-term clinical benefit. 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. Currently, zoledronic acid is the only bisphosphonate that has demonstrated statistically significant reductions in skeletal morbidity – including durable pain reduction – in this patient population in a randomized placebocontrolled trial. Therefore, zoledronic acid therapy should be considered to prevent skeletal morbidity and improve the quality of life of prostate cancer patients with bone metastases.
Introduction
Prostate cancer is one of the most common cancers affecting men worldwide.1 Current cancer statistics estimate that more than 200,000 men are diagnosed with prostate cancer in the US each year,2 and five-year worldwide prevalence is approaching 2.5 million cases.3 Approximately 50% of patients will experience disease recurrence after local therapy consisting of radiation or prostatectomy.4 Although advances in the treatment of prostate cancer have extended life expectancy, 65% to 75% of patients with advanced disease will develop bone metastases, resulting in accelerated bone resorption and a loss of skeletal integrity that is associated with significant skeletal morbidity, including pathologic fractures, spinal cord compression, and debilitating bone pain.5
The incidence of skeletal complications experienced by patients with metastatic prostate cancer is illustrated by the placebo group of a recent study of zoledronic acid in men with hormone-refractory prostate cancer (HRPC) and bone metastases.6,7 In this study, nearly 50% of patients receiving placebo experienced = 1 skeletal complication and 33% suffered severe bone pain requiring palliative radiotherapy. A recent study showed that these skeletal complications result in significant decreases in quality-of-life scores.8 Therefore, therapies that prevent skeletal complications and reduce bone pain could translate into improvements in quality of life.
Bisphosphonates are potent inhibitors of bone resorption that have demonstrated clinical benefit for the treatment of malignant bone disease and are the standard of care for the prevention of skeletal complications in patients with bone metastases from breast cancer.9 Several studies have evaluated the efficacy of bisphosphonates – including etidronate, clodronate, pamidronate, ibandronate, and zoledronic acid – in patients with bone metastases from prostate cancer. However, until the recent trial evaluating the efficacy of zoledronic acid in men with HRPC and bone metastases, no bisphosphonate has demonstrated statistically significant long-term reductions in skeletal morbidity or durable pain reduction in this patient population in a randomized placebo-controlled trial.6
References:
1. Parkin D M, Pisani P and Ferlay J, "Global cancer statistics", C A Cancer J. Clin. (1999), 49: pp. 33-64.
2. Jemal A,Tiwari R C, Murray T, et al., "Cancer statistics, 2004", C A Cancer J. Clin. (2004), 54: pp. 8-29.
3. Ferlay J, Bray F, Pisani P and Parkin D M,"GLOBOCAN 2002: Cancer Incidence, Mortality and Prevalence Worldwide", IARC CancerBase No. 5, version 2.0. Lyon, France: IARC Press, Available at: http://wwwdep. iarc.fr/globocan/GLOBOframe.htm Accessed November 16, 2004.
4. Goodin S, Rao K V and DiPaola R S,"State-of-the-art treatment of metastatic hormone-refractory prostate cancer", Oncologist (2002), 7: pp. 360-370.
5. Coleman R E,"Metastatic bone disease: clinical features, pathophysiology and treatment strategies", Cancer Treat. Rev. (2001), 27: pp. 165-176.
6. Saad F, Gleason D M, Murray R et al., "Long-term efficacy of zoledronic acid for the prevention of skeletal complications in patients with metastatic hormone-refractory prostate cancer", J. Natl. Cancer Inst. (2004), 96: pp. 879-882.
7. Saad F, Gleason D, Murray R et al., "Zoledronic acid is well tolerated for up to 24 months and significantly reduces skeletal complications in patients with advanced prostate cancer metastatic to bone", [poster], Poster presented at: American Urological Association Annual Meeting;April 26 May 1, 2003; Chicago, Illinois. Abstract 1472.
8. Weinfurt K P, Li Y, Castel L D,Timbie J W, Glendenning A and Schulman K A,"The impact of skeletal-related events on healthrelated quality of life of patients with metastatic prostate cancer", [abstract] Ann. Oncol. (2002), 13 (suppl 5): p. 180. Abstract p. 662.
9. Hillner B E, Ingle J N, Chlebowski R T et al., "American Society of Clinical Oncology 2003 update on the role of bisphosphonates and bone health issues in women with breast cancer", [published erratum appears in J. Clin. Oncol. (2004), 22: 1351], J. Clin. Oncol. (2003), 21: pp. 4,042-4,057.
10. Carey P O and Lippert M C,"Treatment of painful prostatic bone metastases with oral etidronate disodium", Urology (1988), 32: pp. 403-407.
11.Kylmälä T,Tammela T L, Lindholm T S and Seppanen J, "The effect of combined intravenous and oral clodronate treatment on bone pain in patients with metastatic prostate cancer", Ann. Chir. Gynaecol. (1994), 83: pp. 316-319.
12. Cresswell S M, English P J, Hall R R, Roberts J T and Marsh M M, "Pain relief and quality-of-life assessment following intravenous and oral clodronate in hormone-escaped metastatic prostate cancer", Br. J. Urol. (1995), 76: pp. 360-365.
13. Heidenreich A, Hofmann R and Engelmann U H, "The use of bisphosphonate for the palliative treatment of painful bone metastasis due to hormone refractory prostate cancer", J. Urol. (2001), 165: pp. 136-140.
14. Elomaa I, Kylmälä T,Tammela T, et al., "Effect of oral clodronate on bone pain. A controlled study in patients with metastatic prostatic cancer", Int. Urol. Nephrol. (1992), 24: pp. 159-166.
15.Kylmälä T,Taube T,Tammela T L, Risteli L, Risteli J and Elomaa I, "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 (1997), 76: pp. 939-942.
16. Strang P, Nilsson S, Brandstedt S, et al.,"The analgesic efficacy of clodronate compared with placebo in patients with painful bone metastases from prostatic cancer", Anticancer Res. (1997), 17: pp. 4,717-4,721.
17. Ernst D S, Tannock I F, Winquist E W, et al., "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. (2003), 21: pp. 3,335-3,342.
18. Dearnaley D , Sydes M R, Mason M D, 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: pp. 1,300-1,311.
19. Lipton A, Glover D, Harvey H, et al.,"Pamidronate in the treatment of bone metastases: results of 2 dose-ranging trials in patients with breast or prostate cancer", Ann. Oncol. (1994), 5 (suppl 7): pp. S31-S35.
20. Small E J, Smith M R, Seaman J J, Petrone S and Kowalski M O,"Combined analysis of two multicenter, randomized, placebocontrolled studies of pamidronate disodium for the palliation of bone pain in men with metastatic prostate cancer", J. Clin. Oncol. (2003), 21: pp. 4,277-4,284.
21. Heidenreich A, Elert A and Hofmann R,"Ibandronate in the treatment of prostate cancer associated painful osseous metastases", Prostate Cancer Prostatic Dis. (2002), 5: pp. 231-235.
22. Saad F, Gleason D M, Murray R, et al., "A randomized, placebo-controlled trial of zoledronic acid in patients with hormonerefractory metastatic prostate carcinoma", For the Zoledronic Acid Prostate Cancer Study Group, J. Nat. Cancer Inst. (2002), 94: pp. 1,458-1,468.
23. Major P P and Cook R,"Efficacy of bisphosphonates in the management of skeletal complications of bone metastases and selection of clinical endpoints", Am. J. Clin. Oncol. (2002), 25 (suppl 1): pp. S10-S18.
24. Lipton A, Small E, Saad F, et al.,"The new bisphosphonate, Zometa (r) (zoledronic acid), decreases skeletal complications in both osteolytic and osteoblastic lesions: a comparison to pamidronate", Cancer Invest. (2002), 20 (suppl 2): pp. 45-54.
25. Saad F, Gleason D, Murray R, et al.,"Early and sustained clinical benefit of zoledronic acid in men with advanced prostate cancer (PC) metastatic to bone: comparison with pamidronate", [poster], Poster presented at: Canadian Urological Association 59th Annual Meeting; June 27 July 1, 2004;Whistler, British Columbia. Abstract 30.
26. Gleason D, Saad F, Goas A and Zheng M, "Continuing benefit of zoledronic acid in preventing skeletal complications after the first occurrence in patients with prostate cancer and bone metastases", [abstract], Proc.Am. Soc. Clin. Oncol. (2003), 22: p. 379, Abstract 1522.
27. Saad F, Gleason D, Murray R, et al., "Long-term reduction of bone pain with zoledronic acid in patients with advanced prostate cancer metastatic to bone", [poster], Poster presented at:American Urological Association Annual Meeting;April 26 May 1, 2003; Chicago, Illinois, Abstract 1473.
28. Major P P, Cook R J, Chen B-L and Zheng M, "Zoledronic acid reduces the need for radiation to bone in patients with breast or prostate cancer metastatic to bone: a survival-adjusted cumulative incidence analysis", [abstract], Proc.Am. Soc. Clin. Oncol. (2004), 23: p. 739, Abstract 8058.
29. Carroll P R, Altwein J, Brawley O, et al., "Management of disseminated prostate cancer", In: Denis L, Bartsch G, Khoury S, et al, (eds), Prostate Cancer: 3rd International Consultation on Prostate Cancer-Paris. Paris: Health Publications; (2003), pp. 251-284.
30. Smith M R, Eastham J, Gleason D M, Shasha D,Tchekmedyian S and 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: pp. 2,008-2,012.
31.Padalecki S S, Carreon M, Grubbs B, Cui Y and Guise T A, "Androgen deprivation enhances bone loss and prostate cancer metastases to bone: prevention by zoledronic acid", Oncology (2003), 17 (suppl 3): p. 32.
2. Jemal A,Tiwari R C, Murray T, et al., "Cancer statistics, 2004", C A Cancer J. Clin. (2004), 54: pp. 8-29.
3. Ferlay J, Bray F, Pisani P and Parkin D M,"GLOBOCAN 2002: Cancer Incidence, Mortality and Prevalence Worldwide", IARC CancerBase No. 5, version 2.0. Lyon, France: IARC Press, Available at: http://wwwdep. iarc.fr/globocan/GLOBOframe.htm Accessed November 16, 2004.
4. Goodin S, Rao K V and DiPaola R S,"State-of-the-art treatment of metastatic hormone-refractory prostate cancer", Oncologist (2002), 7: pp. 360-370.
5. Coleman R E,"Metastatic bone disease: clinical features, pathophysiology and treatment strategies", Cancer Treat. Rev. (2001), 27: pp. 165-176.
6. Saad F, Gleason D M, Murray R et al., "Long-term efficacy of zoledronic acid for the prevention of skeletal complications in patients with metastatic hormone-refractory prostate cancer", J. Natl. Cancer Inst. (2004), 96: pp. 879-882.
7. Saad F, Gleason D, Murray R et al., "Zoledronic acid is well tolerated for up to 24 months and significantly reduces skeletal complications in patients with advanced prostate cancer metastatic to bone", [poster], Poster presented at: American Urological Association Annual Meeting;April 26 May 1, 2003; Chicago, Illinois. Abstract 1472.
8. Weinfurt K P, Li Y, Castel L D,Timbie J W, Glendenning A and Schulman K A,"The impact of skeletal-related events on healthrelated quality of life of patients with metastatic prostate cancer", [abstract] Ann. Oncol. (2002), 13 (suppl 5): p. 180. Abstract p. 662.
9. Hillner B E, Ingle J N, Chlebowski R T et al., "American Society of Clinical Oncology 2003 update on the role of bisphosphonates and bone health issues in women with breast cancer", [published erratum appears in J. Clin. Oncol. (2004), 22: 1351], J. Clin. Oncol. (2003), 21: pp. 4,042-4,057.
10. Carey P O and Lippert M C,"Treatment of painful prostatic bone metastases with oral etidronate disodium", Urology (1988), 32: pp. 403-407.
11.Kylmälä T,Tammela T L, Lindholm T S and Seppanen J, "The effect of combined intravenous and oral clodronate treatment on bone pain in patients with metastatic prostate cancer", Ann. Chir. Gynaecol. (1994), 83: pp. 316-319.
12. Cresswell S M, English P J, Hall R R, Roberts J T and Marsh M M, "Pain relief and quality-of-life assessment following intravenous and oral clodronate in hormone-escaped metastatic prostate cancer", Br. J. Urol. (1995), 76: pp. 360-365.
13. Heidenreich A, Hofmann R and Engelmann U H, "The use of bisphosphonate for the palliative treatment of painful bone metastasis due to hormone refractory prostate cancer", J. Urol. (2001), 165: pp. 136-140.
14. Elomaa I, Kylmälä T,Tammela T, et al., "Effect of oral clodronate on bone pain. A controlled study in patients with metastatic prostatic cancer", Int. Urol. Nephrol. (1992), 24: pp. 159-166.
15.Kylmälä T,Taube T,Tammela T L, Risteli L, Risteli J and Elomaa I, "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 (1997), 76: pp. 939-942.
16. Strang P, Nilsson S, Brandstedt S, et al.,"The analgesic efficacy of clodronate compared with placebo in patients with painful bone metastases from prostatic cancer", Anticancer Res. (1997), 17: pp. 4,717-4,721.
17. Ernst D S, Tannock I F, Winquist E W, et al., "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. (2003), 21: pp. 3,335-3,342.
18. Dearnaley D , Sydes M R, Mason M D, 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: pp. 1,300-1,311.
19. Lipton A, Glover D, Harvey H, et al.,"Pamidronate in the treatment of bone metastases: results of 2 dose-ranging trials in patients with breast or prostate cancer", Ann. Oncol. (1994), 5 (suppl 7): pp. S31-S35.
20. Small E J, Smith M R, Seaman J J, Petrone S and Kowalski M O,"Combined analysis of two multicenter, randomized, placebocontrolled studies of pamidronate disodium for the palliation of bone pain in men with metastatic prostate cancer", J. Clin. Oncol. (2003), 21: pp. 4,277-4,284.
21. Heidenreich A, Elert A and Hofmann R,"Ibandronate in the treatment of prostate cancer associated painful osseous metastases", Prostate Cancer Prostatic Dis. (2002), 5: pp. 231-235.
22. Saad F, Gleason D M, Murray R, et al., "A randomized, placebo-controlled trial of zoledronic acid in patients with hormonerefractory metastatic prostate carcinoma", For the Zoledronic Acid Prostate Cancer Study Group, J. Nat. Cancer Inst. (2002), 94: pp. 1,458-1,468.
23. Major P P and Cook R,"Efficacy of bisphosphonates in the management of skeletal complications of bone metastases and selection of clinical endpoints", Am. J. Clin. Oncol. (2002), 25 (suppl 1): pp. S10-S18.
24. Lipton A, Small E, Saad F, et al.,"The new bisphosphonate, Zometa (r) (zoledronic acid), decreases skeletal complications in both osteolytic and osteoblastic lesions: a comparison to pamidronate", Cancer Invest. (2002), 20 (suppl 2): pp. 45-54.
25. Saad F, Gleason D, Murray R, et al.,"Early and sustained clinical benefit of zoledronic acid in men with advanced prostate cancer (PC) metastatic to bone: comparison with pamidronate", [poster], Poster presented at: Canadian Urological Association 59th Annual Meeting; June 27 July 1, 2004;Whistler, British Columbia. Abstract 30.
26. Gleason D, Saad F, Goas A and Zheng M, "Continuing benefit of zoledronic acid in preventing skeletal complications after the first occurrence in patients with prostate cancer and bone metastases", [abstract], Proc.Am. Soc. Clin. Oncol. (2003), 22: p. 379, Abstract 1522.
27. Saad F, Gleason D, Murray R, et al., "Long-term reduction of bone pain with zoledronic acid in patients with advanced prostate cancer metastatic to bone", [poster], Poster presented at:American Urological Association Annual Meeting;April 26 May 1, 2003; Chicago, Illinois, Abstract 1473.
28. Major P P, Cook R J, Chen B-L and Zheng M, "Zoledronic acid reduces the need for radiation to bone in patients with breast or prostate cancer metastatic to bone: a survival-adjusted cumulative incidence analysis", [abstract], Proc.Am. Soc. Clin. Oncol. (2004), 23: p. 739, Abstract 8058.
29. Carroll P R, Altwein J, Brawley O, et al., "Management of disseminated prostate cancer", In: Denis L, Bartsch G, Khoury S, et al, (eds), Prostate Cancer: 3rd International Consultation on Prostate Cancer-Paris. Paris: Health Publications; (2003), pp. 251-284.
30. Smith M R, Eastham J, Gleason D M, Shasha D,Tchekmedyian S and 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: pp. 2,008-2,012.
31.Padalecki S S, Carreon M, Grubbs B, Cui Y and Guise T A, "Androgen deprivation enhances bone loss and prostate cancer metastases to bone: prevention by zoledronic acid", Oncology (2003), 17 (suppl 3): p. 32.
