Abstract
Ionising radiation is utilised in a variety of situations in the management of prostate cancer. Beyond the scope of this book is the use of brachytherapy and external beam radiotherapy (EBRT) as efficacious, radical treatment modalities in the management of localised prostate cancer. Earlier chapters have covered the use of EBRT as a therapeutic option for the treatment of symptomatic bone metastases. This chapter focuses on the place of radionuclide therapy for the management of bone metastases. Recent development of radium-223 dichloride has reinvigorated this field of therapy. Here, analysis is made of the history of radionuclides and their current role in the modern treatment paradigm; the chapter closes by horizon-scanning for the potential future applications of radionuclide therapy, both as part of novel combinations with other agents and in new settings beyond current licensed indications.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Bibliography
Shiozawa Y, Pedersen EA, Havens AM, Jung Y, Mishra A, Joseph J et al (2011) Human prostate cancer metastases target the hematopoietic stem cell niche to establish footholds in mouse bone marrow. J Clin Invest 121(4):1298–1312
Keller ET, Brown J (2004) Prostate cancer bone metastases promote both osteolytic and osteoblastic activity. J Cell Biochem 91(4):718–729
Atkins GJ, Findlay DM (2012) Osteocyte regulation of bone mineral: a little give and take. Osteoporos Int 23(8):2067–2079
Kassis A, Adelstein SJ (2005) Radiobiologic principles in radionuclide therapy. J Nucl Med 46(no.1 suppl):4s–12s
Sofou S (2008) Radionuclide carriers for targeting of cancer. Int J Nanomedicine 3(2):181–199
Joiner M, Van Der Kogel A (eds) (2009) Basic clinical radiobiology, 4th edn. Hodder Arnold, London
Turner PG, O’Sullivan JM (2015) (223)Ra and other bone-targeting radiopharmaceuticals-the translation of radiation biology into clinical practice. Br J Radiol 88(1050):20140752
Friedell HL, Storaasli JP (1950) The use of radioactive phosphorus in the treatment of carcinoma of the breast with widespread metastases to bone. Am J Roentgenol Radium Ther 64(4):559–575
Nair N (1999) Relative efficacy of 32P and 89Sr in palliation in skeletal metastases. J Nucl Med 40(2):256–261
Finlay IG, Mason MD, Shelley M (2005) Radioisotopes for the palliation of metastatic bone cancer: a systematic review. Lancet Oncol 6(6):392–400
Lewington VJ, McEwan AJ, Ackery DM, Bayly RJ, Keeling DH, Macleod PM et al (1991) A prospective, randomised double-blind crossover study to examine the efficacy of strontium-89 in pain palliation in patients with advanced prostate cancer metastatic to bone. Eur J Cancer 27(8):954–958
Buchali K, Correns HJ, Schuerer M, Schnorr D, Lips H, Sydow K (1988) Results of a double blind study of 89-strontium therapy of skeletal metastases of prostatic carcinoma. Eur J Nucl Med 14(7–8):349–351
Russ Knapp FF Jr, Mirzadeh S, Beets AL, O’Doherty M, Blower PJ, Verdera ES et al (1998) Reactor-produced radioisotopes from ORNL for bone pain palliation. Appl Radiat Isot 49(4):309–315
Palmedo H, Guhlke S, Bender H, Sartor J, Schoeneich G, Risse J et al (2000) Dose escalation study with rhenium-188 hydroxyethylidene diphosphonate in prostate cancer patients with osseous metastases. Eur J Nucl Med 27(2):123–130
O’Sullivan JM, McCready VR, Flux G, Norman AR, Buffa FM, Chittenden S et al (2002) High activity Rhenium-186 HEDP with autologous peripheral blood stem cell rescue: a phase I study in progressive hormone refractory prostate cancer metastatic to bone. Br J Cancer 86(11):1715–1720
O’Sullivan JM, Norman AR, McCready VR, Flux G, Buffa FM, Johnson B et al (2006) A phase 2 study of high-activity 186Re-HEDP with autologous peripheral blood stem cell transplant in progressive hormone-refractory prostate cancer metastatic to bone. Eur J Nucl Med Mol Imaging 33(9):1055–1061
Serafini AN, Houston SJ, Resche I, Quick DP, Grund FM, Ell PJ et al (1998) Palliation of pain associated with metastatic bone cancer using samarium-153 lexidronam: a double-blind placebo-controlled clinical trial. J Clin Oncol 16(4):1574–1581
Sartor O, Reid RH, Hoskin PJ, Quick DP, Ell PJ, Coleman RE et al (2004) Samarium-153-Lexidronam complex for treatment of painful bone metastases in hormone-refractory prostate cancer. Urology 63(5):940–945
Smeland S, Erikstein B, Aas M, Skovlund E, Hess SL, Fossa SD (2003) Role of strontium-89 as adjuvant to palliative external beam radiotherapy is questionable: results of a double-blind randomized study. Int J Radiat Oncol Biol Phys 56(5):1397–1404
Oosterhof GO, Roberts JT, de Reijke TM, Engelholm SA, Horenblas S, von der Maase H et al (2003) Strontium(89) chloride versus palliative local field radiotherapy in patients with hormonal escaped prostate cancer: a phase III study of the European Organisation for Research and Treatment of Cancer Genitourinary Group. Eur Urol 44(5):519–526
Tu S, Millikan RE, Mengistu B, Delpassand ES, Amato RJ, Pagliaro LC et al (2001) Bone-targeted therapy for advanced androgen-independent carcinoma of the prostate: a randomised phase II trial. Lancet 357(9253):336–341
James ND, Sydes MR, Clarke NW, Mason MD, Dearnaley DP, Spears MR et al (2016) 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
Sweeney CJ, Chen YH, Carducci M, Liu G, Jarrard DF, Eisenberger M et al (2015) Chemohormonal therapy in metastatic hormone-sensitive prostate cancer. N Engl J Med 373(8):737–746
Bilen MA, Johnson MM, Mathew P, Pagliaro LC, Araujo JC, Aparicio A et al (2015) Randomized phase 2 study of bone-targeted therapy containing strontium-89 in advanced castrate-sensitive prostate cancer. Cancer 121(1):69–76
Sciuto R, Festa A, Rea S, Pasqualoni R, Bergomi S, Petrilli G et al (2002) Effects of low-dose cisplatin on 89Sr therapy for painful bone metastases from prostate cancer: a randomized clinical trial. J Nuclear Med JNM 43(1):79–86
Lam MG, Bosma TB, van Rijk PP, Zonnenberg BA (2009) (188)Re-HEDP combined with capecitabine in hormone-refractory prostate cancer patients with bone metastases: a phase I safety and toxicity study. Eur J Nucl Med Mol Imaging 36(9):1425–1433
Tannock IF, de Wit R, Berry WR, Horti J, Pluzanska A, Chi KN et al (2004) Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med 351(15):1502–1512
de Bono JS, Oudard S, Ozguroglu M, Hansen S, Machiels JP, Kocak I et al (2010) Prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel treatment: a randomised open-label trial. Lancet 376(9747):1147–1154
van Dodewaard-de Jong JM, de Klerk JM, Bloemendal HJ, van Bezooijen BP, de Haas MJ, Wilson RH et al (2011) A phase I study of combined docetaxel and repeated high activity 186Re-HEDP in castration-resistant prostate cancer (CRPC) metastatic to bone (the TAXIUM trial). Eur J Nucl Med Mol Imaging 38(11):1990–1998
Henriksen G, Fisher DR, Roeske JC, Bruland OS, Larsen RH (2003) Targeting of osseous sites with alpha-emitting 223Ra: comparison with the beta-emitter 89Sr in mice. J Nucl Med 44(2):252–259
Nilsson S, Larsen RH, Fosså SD, Balteskard L, Borch KW, Westlin J et al (2005) First clinical experience with a-emitting radium-223 in the treatment of skeletal metastases. Clin Cancer Res 11(12):4451–4459
Carrasquillo JA, O’Donoghue JA, Pandit-Taskar N, Humm JL, Rathkopf DE, Slovin SF et al (2013) Phase I pharmacokinetic and biodistribution study with escalating doses of (2)(2)(3)Ra-dichloride in men with castration-resistant metastatic prostate cancer. Eur J Nucl Med Mol Imaging 40(9):1384–1393
Nilsson S, Strang P, Aksnes AK, Franzèn L, Olivier P, Pecking A et al (2012) A randomized, dose–response, multicenter phase II study of radium-223 chloride for the palliation of painful bone metastases in patients with castration-resistant prostate cancer. Eur J Cancer 48(5):678–686
Parker CC, Pascoe S, Chodacki A, O’Sullivan JM, Germá JR, O’Bryan-Tear CG et al (2013) A randomized, double-blind, dose-finding, multicenter, phase 2 study of radium chloride (Ra 223) in patients with bone metastases and castration-resistant prostate cancer. Eur Urol 63(2):189–197
Nilsson S, Franzén L, Parker C, Tyrrell C, Blom R, Tennvall J et al (2007) Bone-targeted radium-223 in symptomatic, hormone-refractory prostate cancer: a randomised, multicentre, placebo-controlled phase II study. Lancet Oncol 8(7):587–594
Parker C, Nilsson S, Heinrich D, Helle SI, O’Sullivan JM, Fosså SD, et al (2013; 2015) Alpha emitter radium-223 and survival in metastatic prostate cancer. N Engl J Med 369(3):213–223
Sartor O, Coleman R, Nilsson S, Heinrich D, Helle SI, O’Sullivan JM et al (2014) Effect of radium-223 dichloride on symptomatic skeletal events in patients with castration-resistant prostate cancer and bone metastases: results from a phase 3, double-blind, randomised trial. Lancet Oncol 15(7):738–746
Hoskin P, Sartor O, O’Sullivan JM, Johannessen DC, Helle SI, Logue J et al (2014) Efficacy and safety of radium-223 dichloride in patients with castration-resistant prostate cancer and symptomatic bone metastases, with or without previous docetaxel use: a prespecified subgroup analysis from the randomised, double-blind, phase 3 ALSYMPCA trial. Lancet Oncol 15(12):1397–1406
Chittenden SJ, Hindorf C, Parker CC, Lewington VJ, Pratt BE, Johnson B et al (2015) A Phase 1, open-label study of the biodistribution, pharmacokinetics, and dosimetry of 223Ra-dichloride in patients with hormone-refractory prostate cancer and skeletal metastases. J Nucl Med 56(9):1304–1309
Ryan CJ, Smith MR, Fizazi K, Saad F, Mulders PFA, Sternberg CN et al (2014) Abiraterone acetate plus prednisone versus placebo plus prednisone in chemotherapy-naive men with metastatic castration-resistant prostate cancer (COU-AA-302): final overall survival analysis of a randomised, double-blind, placebo-controlled phase 3 study. The Lancet Oncology Feb 2015;16(2):152–160
de Bono JS, Logothetis CJ, Molina A, Fizazi K, North S, Chu L, et al (2011; 2015) Abiraterone and increased survival in metastatic prostate cancer. N Engl J Med 364(21):1995–2005
Scher HI, Fizazi K, Saad F, Taplin M, Sternberg CN, Miller K, et al (2012; 2015) Increased survival with enzalutamide in prostate cancer after chemotherapy. N Engl J Med 367(13):1187–1197
Beer TM, Armstrong AJ, Rathkopf DE, Loriot Y, Sternberg CN, Higano CS et al (2014; 2015) Enzalutamide in metastatic prostate cancer before chemotherapy. N Engl J Med 371(5):424–433
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2017 Springer International Publishing Switzerland
About this chapter
Cite this chapter
O’Sullivan, J., Turner, P. (2017). Bone-Seeking Radionuclide for Therapy. 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_16
Download citation
DOI: https://doi.org/10.1007/978-3-319-42327-2_16
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-42326-5
Online ISBN: 978-3-319-42327-2
eBook Packages: MedicineMedicine (R0)