Skip to main content

Advertisement

Log in

Factors affecting 223Ra therapy: clinical experience after 532 cycles from a single institution

  • Original Article
  • Published:
European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

The aim of this study was to identify baseline features that predict outcome in 223Ra therapy.

Methods

We retrospectively reviewed 110 patients with metastatic castration-resistant prostate cancer treated with 223Ra. End points were overall survival (OS), progression-free survival (PFS), bone event-free survival (BeFS), and bone marrow failure (BMF). The following parameters were evaluated prior to the first 223Ra cycle: serum levels of hemoglobin (Hb), prostate-specific antigen (PSA), alkaline phosphatase (ALP), Eastern Cooperative Oncology Group (ECOG) status, pain score, use of chemotherapy, and external beam radiation therapy (EBRT). During/after 223Ra we evaluated: the total number of radium cycles (RaTot), the PSA doubling time (PSADT), and the use of chemotherapy, EBRT, abiraterone, and enzalutamide.

Results

A significant reduction of ALP (p < 0.001) and pain score (p = 0.041) occurred throughout the 223 Ra cycles. The risk of progression was associated with declining ECOG status [hazard ratio (HR) = 3.79; p < 0.001] and decrease in PSADT (HR = 8.22; p < 0.001). RaTot, ALP, initial ECOG status, initial pain score, and use of abiraterone were associated with OS (p ≤ 0.008), PFS (p ≤ 0.003), and BeFS (p ≤ 0.020). RaTot, ALP, initial ECOG status, and initial pain score were significantly associated with BMF (p ≤ 0.001) as well as Hb (p < 0.001) and EBRT (p = 0.009). On multivariable analysis, only RaTot and abiraterone remained significantly associated with OS (p < 0.001; p = 0.033, respectively), PFS (p < 0.001; p = 0.041, respectively), and BeFS (p < 0.001; p = 0.019, respectively). Additionally, RaTot (p = 0.027) and EBRT (p = 0.013) remained significantly associated with BMF.

Conclusion

Concomitant use of abiraterone and 223Ra seems to have a beneficial effect, while the EBRT may increase the risk of BMF.

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

Access this article

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
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. 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;15:1397–406. doi:10.1016/s1470-2045(14)70474-7.

    Article  CAS  PubMed  Google Scholar 

  2. Parker C, Nilsson S, Heinrich D, Helle SI, O’Sullivan JM, Fosså SD, et al. Alpha emitter radium-223 and survival in metastatic prostate cancer. N Engl J Med 2013;369:213–23. doi:10.1056/NEJMoa1213755.

    Article  CAS  PubMed  Google Scholar 

  3. Nilsson S, Franzén L, Parker C, Tyrrell C, Blom R, Tennvall J, et al. Two-year survival follow-up of the randomized, double-blind, placebo-controlled phase II study of radium-223 chloride in patients with castration-resistant prostate cancer and bone metastases. Clin Genitourin Cancer 2013;11:20–6. doi:10.1016/j.clgc.2012.07.002.

    Article  PubMed  Google Scholar 

  4. 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;68:42–50. doi:10.1016/j.eururo.2014.10.001.

    Article  PubMed  Google Scholar 

  5. Jadvar H, Challa S, Quinn DI, Conti PS. One-year postapproval clinical experience with radium-223 dichloride in patients with metastatic castrate-resistant prostate cancer. Cancer Biother Radiopharm 2015;30:195–9. doi:10.1089/cbr.2014.1802.

    Article  CAS  PubMed  Google Scholar 

  6. Kelloff GJ, Coffey DS, Chabner BA, Dicker AP, Guyton KZ, Nisen PD, et al. Prostate-specific antigen doubling time as a surrogate marker for evaluation of oncologic drugs to treat prostate cancer. Clin Cancer Res 2004;10:3927–33. doi:10.1158/1078-0432.ccr-03-0788.

    Article  CAS  PubMed  Google Scholar 

  7. Humm JL, Sartor O, Parker C, Bruland OS, Macklis R. Radium-223 in the treatment of osteoblastic metastases: a critical clinical review. Int J Radiat Oncol Biol Phys 2015;91:898–906. doi:10.1016/j.ijrobp.2014.12.061.

    Article  PubMed  Google Scholar 

  8. Den RB, Doyle LA, Knudsen KE. Practical guide to the use of radium 223 dichloride. Can J Urol 2014;21:70–6.

    PubMed  Google Scholar 

  9. Nilsson S, Larsen RH, Fosså SD, Balteskard L, Borch KW, Westlin JE, et al. First clinical experience with alpha-emitting radium-223 in the treatment of skeletal metastases. Clin Cancer Res 2005;11:4451–9. doi:10.1158/1078-0432.ccr-04-2244.

    Article  CAS  PubMed  Google Scholar 

  10. 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;364:1995–2005. doi:10.1056/NEJMoa1014618.

    Article  PubMed Central  PubMed  Google Scholar 

  11. Beckett RD, Rodeffer KM, Snodgrass R. Abiraterone for the treatment of metastatic castrate-resistant prostate cancer. Ann Pharmacother 2012;46:1016–24. doi:10.1345/aph.1Q758.

    Article  PubMed  Google Scholar 

  12. Fizazi K, Scher HI, Molina A, Logothetis CJ, Chi KN, Jones RJ, et al. 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 2012;13:983–92. doi:10.1016/s1470-2045(12)70379-0.

    Article  CAS  PubMed  Google Scholar 

  13. Hingorani M, Dixit S, Pugazhenthi P, Hawkyard S, Robertson A, Khafagy R. Can palliative radiotherapy influence prostate-specific antigen response in patients with castrate-resistant prostate cancer treated with systemic therapy (chemotherapy or abiraterone)?-a report of three cases. Cancer Biol Med 2015;12:60–3. doi:10.7497/j.issn.2095-3941.2014.0025.

    PubMed Central  PubMed  Google Scholar 

  14. Graff JN, Gordon MJ, Beer TM. Safety and effectiveness of enzalutamide in men with metastatic, castration-resistant prostate cancer. Expert Opin Pharmacother 2015;16:749–54. doi:10.1517/14656566.2015.1016911.

    Article  CAS  PubMed  Google Scholar 

  15. Tan PS, Haaland B, Montero AJ, Kyriakopoulos CE, Lopes G. Hormonal therapeutics enzalutamide and abiraterone acetate in the treatment of metastatic castration-resistant prostate cancer (mCRPC) post-docetaxel-an indirect comparison. Clin Med Insights Oncol 2014;8:29–36. doi:10.4137/cmo.s13671.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  16. Yeku O, Slovin SF. Metabolism and pharmacokinetics of radium-223 in prostate cancer. Expert Opin Drug Metab Toxicol 2015;11:843–9. doi:10.1517/17425255.2015.1021332.

    Article  CAS  PubMed  Google Scholar 

  17. Geenen RW, Delaere KP, van Wersch JW. Haematological variables in prostatic carcinoma patients. Acta Urol Belg 1996;64:21–6.

    CAS  PubMed  Google Scholar 

  18. Etchebehere E, Araujo JC, Milton D, Fox P, Swanston N, Macapinlac H, et al. Skeletal tumor burden on baseline 18F-fluoride PET/CT to predict bone marrow failure after radium-223. J Clin Oncol 2015;33:S11012.

    Google Scholar 

Download references

Research funding

This work is supported in part by the James E. Anderson Distinguished Professorship Endowment, by the Cancer Center Support Grant (NCI Grant P30 CA016672), and Fundação Amparo à Pesquisa da Universidade de São Paulo (FAPESP 2014/03317-8).

Compliance with ethical standards

Authors’ disclosures of potential conflicts of interest

All authors declare that they have no conflict of interest. The authors declare no financial (or other) conflict of interest relating to employment or leadership position, consultant or advisory, stock ownership, honoraria, expert testimony, patents, royalties, licenses, or other remuneration.

Ethical approval

This study was approved by the Institutional Review Board (PA14-0848). Waivers of Informed consent and authorization were granted for the retrospective analysis of the imaging data. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. For this type of study formal consent is not required.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Elba C. Etchebehere.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Etchebehere, E.C., Milton, D.R., Araujo, J.C. et al. Factors affecting 223Ra therapy: clinical experience after 532 cycles from a single institution. Eur J Nucl Med Mol Imaging 43, 8–20 (2016). https://doi.org/10.1007/s00259-015-3185-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00259-015-3185-4

Keywords

Navigation