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Bone-Targeted Agents

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Bone Metastases from Prostate Cancer

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Abstract

In the last two decades, bisphosphonates and denosumab have been instrumental in the treatment of patients suffering with prostatic cancer bone metastases [17]. Recently abiraterone and enzalutamide have demonstrated potential beneficial effects on bone metabolism delaying and reducing skeletal complications. Even with recent improvements in medical treatment of skeletal metastases in prostate cancer, the development of effective and precise therapies aimed to improve patients’ prognosis and quality of life remains a clinical challenge.

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References

  1. Advisory Task Force on Bisphosphonate-Related Osteonecrosis of the Jaws, American Association of Oral and Maxillofacial Surgeons (2007) American Association of Oral and Maxillofacial Surgeons position paper on bisphosphonate-related osteonecrosis of the jaws. J Oral Maxillofac Surg 65:369–376

    Article  Google Scholar 

  2. Barrie SE, Potter GA, Goddard PM et al (1994) Pharmacology of novel steroidal inhibitors of cytochrome P450(17) alpha (17 alpha-hydroxylase/C17-20 lyase). J Steroid Biochem Mol Biol 50:267–273

    Article  CAS  PubMed  Google Scholar 

  3. Bedogni A, Fedele S, Bedogni G et al (2014) Staging of jaw osteonecrosis requires computed tomography for accurate definition of the extent of bony disease. Br J Maxillofac Surg 52:603–608

    Article  Google Scholar 

  4. Beer T, Armstrong A, Rathkopf D et al (2014) Enzalutamide in metastatic prostate cancer before chemotherapy. N Engl J Med 371:424–433

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Berenson JR, Stopeck AT. Medication-related osteonecrosis of the jaw in patients with cancer. http://www.uptodate.com/contents/medication-related-osteonecrosis-ofthe jaw-in-patients-with-cancer. Accessed on 28 Jan 2016

  6. Coleman R, Gnant M, Morgan G et al (2012) Effects of bone-targeted agents on cancer progression and mortality. J Natl Cancer Inst 104:1059–1067

    Article  CAS  PubMed  Google Scholar 

  7. Damato K, Gralow J, Hoff A et al (2005) Expert panel recommendations for the prevention, diagnosis, and treatment of osteonecrosis of the jaws. LDA J 64:21–24

    Google Scholar 

  8. De Bono JS, Logothetis CJ, Molina A et al (2011) Abiraterone and increased survival in metastatic prostate cancer. N Engl J Med 364:1995–2005

    Article  PubMed  PubMed Central  Google Scholar 

  9. Dimopoulos MA, Kastritis E, Bamia C et al (2009) Reduction of osteonecrosis of the jaw (ONJ) after implementation of preventive measures in patients with multiple myeloma treated with zoledronic acid. Ann Oncol 20:117–120

    Article  CAS  PubMed  Google Scholar 

  10. Dougall WC, Chaisson M (2006) The RANK/RANKL/OPG triad in cancer-induced bone diseases. Cancer Metastasis Rev 25:541–549

    Article  CAS  PubMed  Google Scholar 

  11. Fedele S, Bedogni G, Scoletta M et al (2015) Up to a quarter of patients with osteonecrosis of the jaw associated with antiresorptive agents remain undiagnosed. Br J Oral Maxillofac Surg 53:13–17

    Article  PubMed  Google Scholar 

  12. Fizazi K, Carducci M, Smith M et al (2011) Denosumab versus zoledronic acid for treatment of bone metastases in men with castration-resistant prostate cancer: a randomised, double-blind study. Lancet 377:813–822

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Fizazi K, Scher HI, Molina A et al (2012) Abiraterone acetate for treatment of metastatic castration-resistant prostate cancer: final overall survival analysis of the COU-AA-301 randomised, double-blind, placebo-controlled phase 3 study. Lancet Oncol 13:983–992

    Article  CAS  PubMed  Google Scholar 

  14. Fizazi K, Scher HI, Saad F et al (2012) Impact of Enzalutamide, an androgen receptor signaling inhibitor, on time to first skeletal related event (SRE) and pain in the phase 3 AFFIRM Study. Ann Oncol 23 abstract 8960

    Google Scholar 

  15. 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  CAS  PubMed  Google Scholar 

  16. 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 

  17. Horwich A, Parker C, de Reijke T et al (2013) Prostate cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 24:106–114

    Google Scholar 

  18. Iranikhah M, Stricker S, Freeman MK (2014) Future of bisphosphonates and denosumab for men with advanced prostate cancer. Cancer Manag Res 6:217–224

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Iuliani M, Pantano F, Buttigliero C et al (2015) Biological and clinical effects of abiraterone on anti-resorptive and anabolic activity in bone microenvironment. Oncotarget 6:12520–12528

    Article  PubMed  PubMed Central  Google Scholar 

  20. James ND, Sydes MR, Clarke NW et al (2015) STAMPEDE investigators. Addition of docetaxel, zoledronic acid, or both to first-line long-term hormone therapy in prostate cancer (STAMPEDE): survival results from an adaptive, multiarm, multistage, platform randomised controlled trial. Lancet 387(10024):1163–1177

    Article  CAS  PubMed  Google Scholar 

  21. Kachnic LA, Pugh SL, Tai P et al (2013) RTOG 0518: randomized phase III trial to evaluate zoledronic acid for prevention of osteoporosis and associated fractures in prostate cancer patients. Prostate Cancer Prostatic Dis 16:382–386

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Lacey DL, Boyle WJ, Simonet WS et al (2012) Bench to bedside: elucidation of the OPG-RANK-RANKL pathway and the development of denosumab. Nat Rev Drug Discov 11:401–419

    Article  CAS  PubMed  Google Scholar 

  23. Li X, Liu Y, Wu B et al (2014) Potential role of the OPG/RANK/RANKL axis in prostate cancer invasion and bone metastasis. Oncol Rep 32:2605–2611

    CAS  PubMed  Google Scholar 

  24. Lipton A, Fizazi K, Stopeck AT et al (2012) Superiority of denosumab to zoledronic acid for prevention of skeletal-related events: a combined analysis of 3 pivotal, randomised, phase 3 trials. Eur J Cancer 48:3082–3092

    Article  CAS  PubMed  Google Scholar 

  25. Liu XH, Kirschenbaum A, Yao S et al (2005) Cross-talk between the interleukin-6 and prostaglandin E(2) signaling systems results in enhancement of osteoclastogenesis through effects on the osteoprotegerin/receptor activator of nuclear factor-{kappa}B (RANK) ligand/RANK system. Endocrinology 146:1991–1998

    Article  CAS  PubMed  Google Scholar 

  26. Logothetis CJ, Basch E, Molina A et al (2012) Effect of abiraterone acetate and prednisone compared with placebo and prednisone on pain control and skeletal-related events in patients with metastatic castration-resistant prostate cancer: exploratory analysis of data from the COU-AA-301 randomised trial. Lancet Oncol 13:1210–1217

    Article  CAS  PubMed  Google Scholar 

  27. Loser K, Mehling A, Loeser S et al (2006) Epidermal RANKL controls regulatory T-cell numbers via activation of dendritic cells. Nat Med 12:1372–1379

    Article  CAS  PubMed  Google Scholar 

  28. Luckman SP, Hughes DE, Coxon FP et al (1998) Nitrogen-containing bisphosphonates inhibit the mevalonate pathway and prevent post-translational prenylation of GTP-binding proteins, including Ras. J Bone Miner Res 13:581–589

    Article  CAS  PubMed  Google Scholar 

  29. Michaelson MD, Kaufman DS, Lee H et al (2007) Randomized controlled trial of annual zoledronic acid to prevent gonadotropin-releasing hormone agonist-induced bone loss in men with prostate cancer. J Clin Oncol 25(9):1038–1042

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Miller RE, Roudier M, Jones J et al (2008) RANK ligand inhibition plus docetaxel improves survival and reduces tumor burden in a murine model of prostate cancer bone metastasis. Mol Cancer Ther 7(7):2160–2169

    Article  CAS  PubMed  Google Scholar 

  31. Mönkkönen H, Auriola S, Lehenkari P et al (2006) A new endogenous ATP analog (ApppI) inhibits the mitochondrial adenine nucleotide translocase (ANT) and is responsible for the apoptosis induced by nitrogen-containing bisphosphonates. Br J Pharmacol 147:437–445

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Nicoletti P, Cartsos VM, Palaska PK et al (2012) Genomewide pharmacogenetics of bisphosphonate-induced osteonecrosis of the jaw: the role of RBMS3. Oncologist 17:279

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. O’Donnell A, Judson I, Dowsett M et al (2004) Hormonal impact of the 17alpha-hydroxylase/C(17,20)-lyase inhibitor abiraterone acetate (CB7630) in patients with prostate cancer. Br J Cancer 90:2317–2325

    PubMed  PubMed Central  Google Scholar 

  34. Rathkopf DE, Smith MR, de Bono JS et al (2014) Updated interim efficacy analysis and long-term safety of abiraterone acetate in metastatic castration-resistant prostate cancer patients without prior chemotherapy (COU-AA-302). Eur Urol 66:815–825

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Ripamonti CI, Cislaghi E, Mariani L et al (2011) Efficacy and safety of medical ozone (03) delivered in oil suspension applications for the treatment of osteonecrosis of the jaw in patients with bone metastases treated with bisphosphonates: Preliminary results of a phase I-II study. Oral Oncol 47:185–190

    Article  CAS  PubMed  Google Scholar 

  36. Ripamonti CI, Maniezzo M, Boldini S et al (2012) Efficacy and tolerability of medical ozone gas insufflations in patients with osteonecrosis of the jaw treated with bisphosphonates-Preliminary data. Med Ozone Gas Insufflat Treat ONJ Lesions J Bone Oncol 1:81–87

    CAS  Google Scholar 

  37. Ripamonti CI, Maniezzo M, Campa T et al (2009) Decreased occurrence of osteonecrosis of the jaw after implementation of dental preventive measures in solid tumor patients with bone metastases treated with bisphosphonates. The experience of the National Cancer Institute of Milano. Ann Oncol 20(1):137–145

    Article  CAS  PubMed  Google Scholar 

  38. Roelofs AJ, Thompson K, Gordon S et al (2006) Molecular mechanisms of action of bisphosphonates: current status. Clin Cancer Res 12:6222s–6230s

    Article  CAS  PubMed  Google Scholar 

  39. Ruggiero RL et al (2014) American association of oral and maxillofacial surgeons position paper on medication-related osteonecrosis of the jaw-2014 update. J Oral Maxillofac Surg 72/10:1938–1956

    Article  Google Scholar 

  40. Ruggiero S, Gralow J, Marx RE et al (2006) Practical guidelines for the prevention, diagnosis, and treatment of osteonecrosis of the jaw in patients with cancer. J Oncol Pract 2(1):7–14

    Article  PubMed  PubMed Central  Google Scholar 

  41. Ruggiero SL, Dodson TB, Assael LA et al (2009) American Association of oral and maxillofacial surgeons position paper on bisphosphonate-related osteonecrosis of the jaw-2009 update. J Oral Maxillofac Surg 67(Suppl 5):2–12

    PubMed  Google Scholar 

  42. Ryan CJ, Smith MR, de Bono JS et al (2013) Abiraterone in metastatic prostate cancer without previous chemotherapy. N Engl J Med 368:138–148

    Article  CAS  PubMed  Google Scholar 

  43. Saad F, Brown JE, Poznack V et al (2012) Incidence, risk factors, and outcome of osteonecrosis of the jaw: integrated analysis from three blinded active-controlled phase III trials in cancer patients with bone metastases. Ann Oncol 23:1341–1347

    Article  CAS  PubMed  Google Scholar 

  44. Saad F, Gleason DM, Murray R et al (2002) A randomized, placebo-controlled trial of zoledronic acid in patients with hormone refractory metastatic prostate carcinoma. J Natl Cancer Inst 94(19):1458–1468

    Article  CAS  PubMed  Google Scholar 

  45. 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 carcinoma. J Natl Cancer Inst 96(11):879–882

    Article  CAS  PubMed  Google Scholar 

  46. Saad F, Shore N, Van Poppel H et al (2015) Impact of bone-targeted therapies in chemotherapy-naïve metastatic castration-resistant prostate cancer patients treated with abiraterone acetate: post hoc analysis of study COU-AA-302. Eur Urol 68(4):570–577

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Santini D, Perrone G, Roato I et al (2011) Expression pattern of receptor activator of NFkB (RANK) in a series of primary solid tumors and related bone metastases. J Cell Physiol 226:780–784

    Article  CAS  PubMed  Google Scholar 

  48. Scher HI, Fizazi K, Saad F et al; AFFIRM Investigators (2012) Increased survival with enzalutamide in prostate cancer after chemotherapy. N Engl J Med 367(13):1187–1197

    Google Scholar 

  49. Scoletta M, Arduino PG, Reggio L et al (2010) Effect of low-level laser irradiation on bisphosphonate-induced osteonecrosis of the jaws: preliminary results of a prospective study. Photomed Laser Surg 28:179

    Article  CAS  PubMed  Google Scholar 

  50. Small EJ, Smith MR, Seaman JJ et al (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 21:4277e–4284e

    Article  CAS  Google Scholar 

  51. Smith MR, Eastham J, Gleason DM et al (2003) Randomized controlled trial of zoledronic acid to prevent bone loss in men receiving androgen deprivation therapy for nonmetastatic prostate cancer. J Urol 169(6):2008–2012

    Article  CAS  PubMed  Google Scholar 

  52. Smith MR, Egerdie B, Hemdezet TN et al (2009) Denosumab in men receiving androgen-deprivation therapy for prostate cancer. N Engl J Med 361:745–755

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Smith MR, Halabi S, Ryan CJ et al (2014) Randomized controlled trial of early zoledronic acid in men with castration-sensitive prostate cancer and bone metastases: results of CALGB 90202 (Alliance). J Clin Oncol 32(11):1143–1150

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Smith MR, Saad F, Egerdie B et al (2009) Effects of denosumab on bone mineral density in men receiving androgen deprivation therapy for prostate cancer. J Urol 182:2670–2675

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Smith MR, Saad F, Oudard S et al (2013) Denosumab and bone metastasis-free survival in men with nonmetastatic castration-resistant prostate cancer: exploratory analyses by baseline prostate-specific antigen doubling time. J Clin Oncol 31(30):3800–3806

    Article  PubMed  PubMed Central  Google Scholar 

  56. Van Beek E, Pieterman E, Cohen L et al (1999) Nitrogen-containing bisphosphonates inhibit isopentenyl pyrophosphate isomerase/farnesyl pyrophosphate synthase activity with relative potencies corresponding to their antiresorptive potencies in vitro and in vivo. Biochem Biophys Res Commun 255(2):491

    Article  PubMed  Google Scholar 

  57. Vescovi P, Campisi G, Fusco V et al (2011) Surgery-triggered and non surgery-triggered Bisphosphonates-related Osteonecrosis of the Jaws (BRONJ): a retrospective analysis of 567 cases in an Italian multi center study. Oral Oncol 47(3):191–194

    Article  CAS  PubMed  Google Scholar 

  58. Vescovi P, Merigo E, Manfredi M et al (2008) Nd:YAG laser biostimulation in the treatment of bisphosphonate-associated osteonecrosis of the jaw: clinical experience in 28 cases. Photomed Laser Surg 26:37

    Article  PubMed  Google Scholar 

  59. Weitzman R, Sauter N, Eriksen EF et al (2007) Critical review: updated recommendations for the prevention, diagnosis and treatment of osteonecrosis of the jaw in cancer patients. Crit Rev Oncol Hematol 62(2):148–152

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Medical Oncology, Campus Bio-Medico University of Rome, Rome, Italy

    Daniele Santini, Alice Zoccoli, Michele Iuliani, Marco Fioramonti, Giulia Ribelli & Francesco Pantano

  2. Supportive Care in Cancer Unit, Fondazione IRCCS, Istituto Nazionale dei Tumori, Milan, Italy

    Carla Ripamonti

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  1. Daniele Santini
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  2. Carla Ripamonti
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  3. Alice Zoccoli
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  4. Michele Iuliani
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  5. Marco Fioramonti
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  7. Francesco Pantano
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Correspondence to Daniele Santini .

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Editors and Affiliations

  1. University of Verona, Director of Metabolic Bone Diseases and Osteoncology Unit, Internal Medicine Department of Medicine, Verona, Italy

    Francesco Bertoldo

  2. IRCCS AOU San Martino-IST National Cancer Research Institute, Department of Internal Medicine and Medical specialties (DIMI), School of Medical and Pharmacological Sciences, University of Genoa, Academic Unit of Medical Oncology, Department of Oncology (DIPOE), Genoa, Italy

    Francesco Boccardo

  3. Humanitas Gavazzeni Clinic, Clical Scientific Director Department of Nuclear Medicine, Bergamo, Italy

    Emilio Bombardieri

  4. Veneto Institute of Oncology IOV - IRCCS, Nuclear Medicine and Molecular imaging Unit, Padova, Italy

    Laura Evangelista

  5. Radiation Oncology 1 and Prostate Cancer Program, Fondazione IRCCS Istituto Nazionale dei Tumori, Department of Oncology and Hemato-oncology, UniversitĂ  di Milano, Milan, Italy

    Riccardo Valdagni

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Santini, D. et al. (2017). Bone-Targeted Agents. In: Bertoldo, F., Boccardo, F., Bombardieri, E., Evangelista, L., Valdagni, R. (eds) Bone Metastases from Prostate Cancer . Springer, Cham. https://doi.org/10.1007/978-3-319-42327-2_15

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  • DOI: https://doi.org/10.1007/978-3-319-42327-2_15

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