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Radiopharmaceutical Therapy in Metastatic CRPC

  • Kwang Suk Lee
  • Byung Ha Chung
Chapter

Abstract

Radiopharmaceuticals are used in the treatment of metastatic castration-resistant prostate cancer. In the United States, four bone-seeking radiopharmaceuticals have been approved. Three of these are β-emitters approved for palliative purposes (phosphorus-32, strontium-89, samarium-153-ethylenediamine tetramethylene phosphonic acid). One α-emitter (radium-223) has been approved for prolonged survival in patients with metastatic prostate cancer. Radiopharmaceuticals for bones have been used for decades in combination with chemotherapy, hormones, and bisphosphonates. Current combinations and clinical trials focus primarily on radium-223, assuming that overall survival benefit is related to this radionuclide. In this chapter, the radiopharmaceutical treatment methods will be elaborated.

Keywords

Prostate cancer Castration-resistant Clinical trial Drug CRPC 

References

  1. 1.
    Tannock IF, de Wit R, Berry WR, Horti J, Pluzanska A, Chi KN, et al. Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med. 2004;351(15):1502–12.CrossRefPubMedGoogle Scholar
  2. 2.
    de Bono JS, Oudard S, Ozguroglu M, Hansen S, Machiels JP, Kocak I, et al. Prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel treatment: a randomised open-label trial. Lancet. 2010;376(9747):1147–54.CrossRefPubMedGoogle Scholar
  3. 3.
    Beer TM, Armstrong AJ, Rathkopf DE, Loriot Y, Sternberg CN, Higano CS, et al. Enzalutamide in metastatic prostate cancer before chemotherapy. N Engl J Med. 2014;371(5):424–33.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    de Bono JS, Logothetis CJ, Molina A, Fizazi K, North S, Chu L, et al. Abiraterone and increased survival in metastatic prostate cancer. N Engl J Med. 2011;364(21):1995–2005.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Ryan CJ, Smith MR, de Bono JS, Molina A, Logothetis CJ, de Souza P, et al. Abiraterone in metastatic prostate cancer without previous chemotherapy. N Engl J Med. 2013;368(2):138–48.CrossRefPubMedGoogle Scholar
  6. 6.
    Scher HI, Fizazi K, Saad F, Taplin ME, Sternberg CN, Miller K, et al. Increased survival with enzalutamide in prostate cancer after chemotherapy. N Engl J Med. 2012;367(13):1187–97.CrossRefPubMedGoogle Scholar
  7. 7.
    Parker C, Nilsson S, Heinrich D, Helle SI, O'Sullivan JM, Fossa SD, et al. Alpha emitter radium-223 and survival in metastatic prostate cancer. N Engl J Med. 2013;369(3):213–23.CrossRefPubMedGoogle Scholar
  8. 8.
    Baldari S, Boni G, Bortolus R, Caffo O, Conti G, De Vincentis G, et al. Management of metastatic castration-resistant prostate cancer: a focus on radium-223: opinions and suggestions from an expert multidisciplinary panel. Crit Rev Oncol Hematol. 2017;113:43–51.CrossRefPubMedGoogle Scholar
  9. 9.
    Saad F, Clarke N, Colombel M. Natural history and treatment of bone complications in prostate cancer. Eur Urol. 2006;49(3):429–40.CrossRefPubMedGoogle Scholar
  10. 10.
    van Dodewaard-de Jong JM, Verheul HM, Bloemendal HJ, de Klerk JM, Carducci MA, van den Eertwegh AJ. New treatment options for patients with metastatic prostate cancer: what is the optimal sequence? Clin Genitourin Cancer. 2015;13(4):271–9.CrossRefPubMedGoogle Scholar
  11. 11.
    Mercadante S. Malignant bone pain: pathophysiology and treatment. Pain. 1997;69(1–2):1–18.CrossRefPubMedGoogle Scholar
  12. 12.
    Lam MG, de Klerk JM, van Rijk PP, Zonnenberg BA. Bone seeking radiopharmaceuticals for palliation of pain in cancer patients with osseous metastases. Anti Cancer Agents Med Chem. 2007;7(4):381–97.CrossRefGoogle Scholar
  13. 13.
    Smart JG. The use of P32 in the treatment of severe pain from bone metastases of carcinoma of the prostate. Br J Urol. 1965;37:139–47.CrossRefPubMedGoogle Scholar
  14. 14.
    Porter AT, McEwan AJ, Powe JE, Reid R, McGowan DG, Lukka H, et al. Results of a randomized phase-III trial to evaluate the efficacy of strontium-89 adjuvant to local field external beam irradiation in the management of endocrine resistant metastatic prostate cancer. Int J Radiat Oncol Biol Phys. 1993;25(5):805–13.CrossRefPubMedGoogle Scholar
  15. 15.
    Serafini AN, Houston SJ, Resche I, Quick DP, Grund FM, Ell PJ, et al. Palliation of pain associated with metastatic bone cancer using samarium-153 lexidronam: a double-blind placebo-controlled clinical trial. J Clin Oncol. 1998;16(4):1574–81.CrossRefPubMedGoogle Scholar
  16. 16.
    Sartor O, Reid RH, Hoskin PJ, Quick DP, Ell PJ, Coleman RE, et al. Samarium-153-Lexidronam complex for treatment of painful bone metastases in hormone-refractory prostate cancer. Urology. 2004;63(5):940–5.CrossRefPubMedGoogle Scholar
  17. 17.
    Sartor O, Hoskin P, Bruland OS. Targeted radio-nuclide therapy of skeletal metastases. Cancer Treat Rev. 2013;39(1):18–26.CrossRefPubMedGoogle Scholar
  18. 18.
    Carrasquillo JA, O'Donoghue JA, Pandit-Taskar N, Humm JL, Rathkopf DE, Slovin SF, et al. 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. 2013;40(9):1384–93.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Dauer LT, Williamson MJ, Humm J, O’Donoghue J, Ghani R, Awadallah R, et al. Radiation safety considerations for the use of (2)(2)(3)RaCl(2) DE in men with castration-resistant prostate cancer. Health Phys. 2014;106(4):494–504.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Hoskin P, Sartor O, O'Sullivan JM, Johannessen DC, Helle SI, Logue J, et al. 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. 2014;15(12):1397–406.CrossRefPubMedGoogle Scholar
  21. 21.
    Nilsson S, Cislo P, Sartor O, Vogelzang NJ, Coleman RE, O’Sullivan JM, et al. Patient-reported quality-of-life analysis of radium-223 dichloride from the phase III ALSYMPCA study. Ann Oncol. 2016;27(5):868–74.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Sartor O, Hoskin P, Coleman RE, Nilsson S, Vogelzang NJ, Petrenciuc O, et al. Chemotherapy following radium-223 dichloride treatment in ALSYMPCA. Prostate. 2016;76(10):905–16.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Lecouvet FE, Geukens D, Stainier A, Jamar F, Jamart J, d'Othee BJ, et al. Magnetic resonance imaging of the axial skeleton for detecting bone metastases in patients with high-risk prostate cancer: diagnostic and cost-effectiveness and comparison with current detection strategies. J Clin Oncol. 2007;25(22):3281–7.CrossRefPubMedGoogle Scholar
  24. 24.
    Padhani AR, Makris A, Gall P, Collins DJ, Tunariu N, de Bono JS. Therapy monitoring of skeletal metastases with whole-body diffusion MRI. J Magn Reson Imaging. 2014;39(5):1049–78.CrossRefPubMedGoogle Scholar
  25. 25.
    Fizazi K, Massard C, Smith M, Rader M, Brown J, Milecki P, et al. Bone-related parameters are the main prognostic factors for overall survival in men with bone metastases from castration-resistant prostate cancer. Eur Urol. 2015;68(1):42–50.CrossRefPubMedGoogle Scholar
  26. 26.
    Parker C, Finkelstein SE, Michalski JM, O'Sullivan JM, Bruland O, Vogelzang NJ, et al. Efficacy and safety of Radium-223 dichloride in symptomatic castration-resistant prostate cancer patients with or without baseline opioid use from the phase 3 ALSYMPCA trial. Eur Urol. 2016;70(5):875–83.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2018

Authors and Affiliations

  1. 1.Department of UrologyYonsei University College of MedicineSeoulSouth Korea

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