Skip to main content
SpringerLink
Log in

A Retrospective Analysis of the First 41 mCRPC Patients with Bone Pain Treated with Radium-223 at the National Institute of Oncology in Hungary

  • Original Article
  • Published:
Pathology & Oncology Research

Abstract

Radium-223 dichloride is an alpha-emitting radiopharmaceutical which significantly prolongs overall survival in patients with castration-resistant prostate cancer (CRPC) and symptomatic bone metastases. This was a retrospective analysis of the efficacy and safety of Radium-223 in the first 41 patients treated at a single center in Hungary. Radium-223 was given at a dose of 50 kBq/kg intravenously every 4 weeks for up to 6 cycles. Between 23rd July 2014 and 23rd February 2016, 41 patients were treated. Patient demographics, laboratory values, treatment outcomes and adverse events were collected from medical records. The mean age was 72.2 years (SD: 7.1). 24 patients received Radium-223 as first-line treatment (58%), 7 patients as second (17%), 3 as third (7.3%), 6 as (14.6%), and 1 as fifth-line therapy (2.4%). The mean number of cycles administered was 5.5 (SD: 1.1). The most common side effects were anemia (32% grade 1–3), nausea (28%, grade 1), diarrhea (4%, grade 2), thrombocytopenia (4%, grade 3). The mean baseline PSA level was 307.2 ng/ml (SD: 525.7), which increased to a mean value of 728.5 ng/ml (SD: 1277) by the end of treatment. The baseline mean ALP of 521.1 U/L (SD: 728) decreased to 245.1 U/L (SD: 283.5). The majority of patients experienced a decrease (37%) or complete cessation (43%) of bone pain intensity. In our symptomatic prostate cancer patient population, Radium-223 proved to be efficient in terms of pain relief, with moderate side effects. No PSA response was detected, while alkaline phosphatase levels significantly decreased.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Hotte SJ, Saad F (2010) Current management of castrate-resistant prostate cancer. Curr Oncol 17(Suppl 2):S72–S79

    PubMed  PubMed Central  Google Scholar 

  2. Saad F, Chi KN, Finelli A, Hotte SJ, Izawa J, Kapoor A, Kassouf W, Loblaw A, North S, Rendon R, So A, Usmani N, Vigneault E, Fleshner NE (2015) The 2015 CUA-CUOG guidelines for the management of castration-resistant prostate cancer (CRPC). Can Urol Assoc J 9(3–4):90–96. doi:10.5489/cuaj.2526

    Article  PubMed  PubMed Central  Google Scholar 

  3. Attard G, Parker C, Eeles RA, Schröder F, Tomlins SA, Tannock I, Drake CG, de Bono JS (2016) Prostate cancer. Lancet 387(10013):70–82

    Article  PubMed  Google Scholar 

  4. DePuy V, Anstrom KJ, Castel LD, Schulman KA, Weinfurt KP, Saad F (2007) Effects of skeletal morbidities on longitudinal patient-reported outcomes and survival in patients with metastatic prostate cancer. Support Care Cancer 15(7):869–876

    Article  PubMed  Google Scholar 

  5. Bubendorf L, Schöpfer A, Wagner U, Sauter G, Moch H, Willi N, Gasser TC, Mihatsch MJ (2000) Metastatic patterns of prostate cancer: an autopsy study of 1,589 patients. Hum Pathol 31(5):578–583

    Article  CAS  PubMed  Google Scholar 

  6. Pelger RC, Soerdjbalie-Maikoe V, Hamdy N (2001) Strategies for management of prostate cancer-related bone pain. Drugs Aging 18(12):899–911

    Article  CAS  PubMed  Google Scholar 

  7. Sartor O, Coleman R, Nilsson S, Heinrich D, Helle SI, O'Sullivan JM, Fosså SD, Chodacki A, Wiechno P, Logue J, Widmark A, Johannessen DC, Hoskin P, James ND, Solberg A, Syndikus I, Vogelzang NJ, O'Bryan-Tear CG, Shan M, Bruland ØS, Parker C (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. doi:10.1016/S1470-2045(14)70183-4

    Article  CAS  PubMed  Google Scholar 

  8. Nilsson S (2016) Radionuclide therapies in prostate cancer: integrating radium-223 in the treatment of patients with metastatic castration-resistant prostate cancer. Curr Oncol Rep 18(2):14. doi:10.1007/s11912-015-0495-4

    Article  PubMed  PubMed Central  Google Scholar 

  9. Shore N (2015) Radium-223 dichloride for metastatic castration-resistant prostate cancer: the urologist's perspective. Urology 85(4):717–724. doi:10.1016/j.urology.2014.11.031

    Article  PubMed  Google Scholar 

  10. Kerr C (2002) (223)Ra targets skeletal metastases and spares normal tissue. Lancet Oncol 3(8):453

    Article  PubMed  Google Scholar 

  11. Bruland ØS, Nilsson S, Fisher DR, Larsen RH (2006) High-linear energy transfer irradiation targeted to skeletal metastases by the alpha-emitter 223Ra: adjuvant or alternative to conventional modalities? Clin Cancer Res 12(20 Pt 2):6250s–6257s

    Article  CAS  PubMed  Google Scholar 

  12. Henriksen G, Breistøl K, Bruland ØS, Fodstad Ø, Larsen RH (2002) Significant antitumor effect from bone-seeking, alpha-particle-emitting (223)Ra demonstrated in an experimental skeletal metastases model. Cancer Res 62(11):3120–3215

    CAS  PubMed  Google Scholar 

  13. Dorff TB, Gross ME (2015) Radium 223: how can we optimize this new tool for metastatic castration-resistant prostate cancer? Am Soc Clin Oncol Educ Book:e270–e273. doi:10.14694/EdBook_AM.2015.35.e270

  14. Nilsson S, Strang P, Aksnes AK, Franzèn L, Olivier P, Pecking A, Staffurth J, Vasanthan S, Andersson C, Bruland ØS (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. doi:10.1016/j.ejca.2011.12.023

    Article  CAS  PubMed  Google Scholar 

  15. Jadvar H, Quinn DI (2013) Targeted α-particle therapy of bone metastases in prostate cancer. Clin Nucl Med 38(12):966–971. doi:10.1097/RLU.0000000000000290

    PubMed  Google Scholar 

  16. Brady D, Parker CC, O'Sullivan JM (2013) Bone-targeting radiopharmaceuticals including radium-223. Cancer J 19(1):71–78. doi:10.1097/PPO.0b013e318282479

    Article  CAS  PubMed  Google Scholar 

  17. Lien LM, Tvedt B, Heinrich D (2015) Treatment of castration-resistant prostate cancer and bone metastases with radium-223 dichloride. Int J Urol Nurs 9(1):3–13

    Article  PubMed  Google Scholar 

  18. McGann S, Horton ER (2015) Radium-223 dichloride: a novel treatment option for castration-resistant prostate cancer patients with symptomatic bone metastases. Ann Pharmacother 49(4):469–476. doi:10.1177/1060028014565444

    Article  CAS  PubMed  Google Scholar 

  19. Parker C, Nilsson S, Heinrich D, Helle SI, O'Sullivan JM, Fosså SD, Chodacki A, Wiechno P, Logue J, Seke M, Widmark A, Johannessen DC, Hoskin P, Bottomley D, James ND, Solberg A, Syndikus I, Kliment J, Wedel S, Boehmer S, Dall'Oglio M, Franzén L, Coleman R, Vogelzang NJ, O'Bryan-Tear CG, Staudacher K, Garcia-Vargas J, Shan M, Bruland ØS, Sartor O, Investigators ALSYMPCA (2013) Alpha emitter radium-223 and survival in metastatic prostate cancer. N Engl J Med 369(3):213–223. doi:10.1056/NEJMoa1213755

    Article  CAS  PubMed  Google Scholar 

  20. Bayer Pharma AG (2015) Xofigo® (radium Ra 223 dichloride) solution for injection Summary of Product Characteristics (SmPC) http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/203971lbl.pdf

  21. Nilsson S (2015) Radium-223 dichloride for the treatment of bone metastatic castration-resistant prostate cancer: an evaluation of its safety. Expert Opin Drug Saf 14(7):1127–2236. doi:10.1517/14740338.2015.1045874

    Article  CAS  PubMed  Google Scholar 

  22. Modi D, Hwang C, Mamdani H, Kim S, Gayar H, Vaishampayan U, Joyrich R, Heath EI (2016) Radium-223 in heavily pretreated metastatic castrate-resistant prostate cancer. Clin Genitourin Cancer . doi:10.1016/j.clgc.2016.03.002pii: S1558-7673(16)30056-8

    Google Scholar 

  23. Hoskin P, Sartor O, O'Sullivan JM, Johannessen DC, Helle SI, Logue J, Bottomley D, Nilsson S, Vogelzang NJ, Fang F, Wahba M, Aksnes AK, Parker C (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. doi:10.1016/S1470-2045(14)70474-7

    Article  CAS  PubMed  Google Scholar 

  24. Autio KA, Bennett AV, Jia X, Fruscione M, Beer TM, George DJ, Carducci MA, Logothetis CJ, Kane RC, Sit L, Rogak L, Morris MJ, Scher HI, Basch EM (2013) Prevalence of pain and analgesic use in men with metastatic prostate cancer using a patient-reported outcome measure. J Oncol Pract 9(5):223–229. doi:10.1200/JOP.2013.000876

    Article  PubMed  PubMed Central  Google Scholar 

  25. Salvati M, Frati A, Russo N, Brogna C, Piccirilli M, D'Andrea G, Occhiogrosso G, Pichierri A, Caroli E (2005) Brain metastasis from prostate cancer. Report of 13 cases and critical analysis of the literature. J Exp Clin Cancer Res 24(2):203–207

    CAS  PubMed  Google Scholar 

  26. Gavrilovic IT, Posner JB (2005) Brain metastases: epidemiology and pathophysiology. J Neuro-Oncol 75(1):5–14

    Article  Google Scholar 

  27. Caffo O, Gernone A, Ortega C, Sava T, Cartenì G, Facchini G, Re GL, Amadio P, Bortolus R, Pagliarulo V, Prati V, Veccia A, Galligioni E (2012) Central nervous system metastases from castration-resistant prostate cancer in the docetaxel era. J Neuro-Oncol 107:191–196

    Article  Google Scholar 

  28. Caffo O, Veccia A, Russo L, Galligioni E (2012) Brain metastases from prostate cancer. Future Oncol 8(12):1585–1595

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. National Institute of Oncology, Ráth György u. 7-9, Budapest, H-1122, Hungary

    Zs Küronya, I Sinkovics, P Ágoston, K Bíró, I Bodrogi, F Gyergyay, T Vajdics, K Nagyiványi & L Géczi

  2. Jahn Ferenc South-Pest Hospital, Budapest, Hungary

    I Böde

  3. 1st Department of Internal Medicine, Semmelweis University, Budapest, Hungary

    M Dank

  4. Teaching Hospital Mór Kaposi, Kaposvár, Hungary

    Zs Kolonics & Á Rúzsa

Authors
  1. Zs Küronya
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. I Sinkovics
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. P Ágoston
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. K Bíró
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. I Bodrogi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. I Böde
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. M Dank
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. F Gyergyay
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. T Vajdics
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Zs Kolonics
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. K Nagyiványi
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Á Rúzsa
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. L Géczi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Zs Küronya.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Küronya, Z., Sinkovics, I., Ágoston, P. et al. A Retrospective Analysis of the First 41 mCRPC Patients with Bone Pain Treated with Radium-223 at the National Institute of Oncology in Hungary. Pathol. Oncol. Res. 23, 777–783 (2017). https://doi.org/10.1007/s12253-017-0190-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12253-017-0190-x

Keywords

Search

Navigation