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Radium-223 Dichloride: A Review of Its Use in Patients with Castration-Resistant Prostate Cancer with Symptomatic Bone Metastases

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Abstract

Radium-223 dichloride (Xofigo®; formerly Alpharadin™) [hereafter referred to as radium-223] is a first-in-class alpha particle-emitting radiopharmaceutical that has recently been approved for the treatment of patients with castration-resistant prostate cancer (CRPC) with symptomatic bone metastases and no known visceral metastatic disease. Radium-223 is a calcium mimetic, which targets bone, delivering cytotoxic radiation to the sites of bone metastases. In the recently reported Alpharadin™ in Symptomatic Prostate Cancer (ALSYMPCA) phase III study, radium-223 was associated with significantly improved overall survival compared with placebo, making it the first bone-targeted CRPC therapy for which an overall survival benefit has been demonstrated. The ALSYMPCA study also demonstrated the beneficial effects of radium-223 on disease-related symptomatic skeletal events, pain and health-related quality of life. Radium-223 was generally well tolerated, being associated with low rates of myelosuppression and generally mild gastrointestinal adverse events. Thus, radium-223 is a valuable addition to the treatment options for this poor-prognosis population.

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References

  1. Jemal A, Bray F, Center MM, et al. Global cancer statistics. CA Cancer J Clin. 2011;61(2):69–90.

    Article  PubMed  Google Scholar 

  2. Kirby M, Hirst C, Crawford ED. Characterising the castration-resistant prostate cancer population: a systematic review. Int J Clin Pract. 2011;65(11):1180–92.

    Article  PubMed  CAS  Google Scholar 

  3. Alva A, Hussain M. The changing natural history of metastatic prostate cancer. Cancer J. 2013;19(1):19–24.

    Article  PubMed  Google Scholar 

  4. Carles J, Castellano D, Climent MÁ, et al. Castration-resistant metastatic prostate cancer: current status and treatment possibilities. Clin Transl Oncol. 2012;14(3):169–76.

    Article  PubMed  CAS  Google Scholar 

  5. El-Amm J, Aragon-Ching JB. The changing landscape in the treatment of metastatic castration-resistant prostate cancer. Ther Adv Med Oncol. 2013;5(1):25–40.

    Article  PubMed Central  PubMed  Google Scholar 

  6. Mukherji D, Eichholz A, De Bono JS. Management of metastatic castration-resistant prostate cancer: recent advances. Drugs. 2012;72(8):1011–28.

    Article  PubMed  CAS  Google Scholar 

  7. Pochon S. Drugs in clinical development for prostate cancer: summary and table. Pharm Med. 2011;25(6):387–404.

    Article  Google Scholar 

  8. Amaral TMS, Macedo D, Fernandes I, et al. Castration-resistant prostate cancer: mechanisms, targets, and treatment. Prostate Cancer. 2012;2012(327253):1–11.

    Article  Google Scholar 

  9. Cookson MS, Roth BJ, Dahm P, et al. Castration-resistant prostate cancer: AUA guideline. J Urol. 2013;190(2):429–38.

    PubMed  Google Scholar 

  10. Omlin A, Pezaro C, Mukherji D, et al. Improved survival in a cohort of trial participants with metastatic castration-resistant prostate cancer demonstrates the need for updated prognostic nomograms. Eur Urol. 2013;64(2):300–6.

    PubMed  Google Scholar 

  11. Saylor PJ, Lee RJ, Smith MR. Emerging therapies to prevent skeletal morbidity in men with prostate cancer. J Clin Oncol. 2011;29(27):3705–14.

    Article  PubMed Central  PubMed  Google Scholar 

  12. Lange PH, Vessella RL. Mechanisms, hypotheses and questions regarding prostate cancer micrometastases to bone. Cancer Metastasis Rev. 1999;17(4):331–6.

    Article  CAS  Google Scholar 

  13. Saad F, Hotte SJ. Guidelines for the management of castrate-resistant prostate cancer. Can Urol Assoc J. 2010;4(6):380–4.

    Article  PubMed Central  PubMed  Google Scholar 

  14. Lewington VJ. Bone-seeking radionuclides for therapy. J Nucl Med. 2005;46(1 Suppl):38S–47S.

    PubMed  CAS  Google Scholar 

  15. Lewis B, Sartor O. Radiation-based approaches for therapy and palliation of advanced prostate cancer. Curr Opin Urol. 2012;22(3):183–9.

    Article  PubMed  Google Scholar 

  16. US FDA. Xofigo (radium Ra 223 dichloride) injection: prescribing information. http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/203971lbl.pdf. Accessed 24 Feb 2014.

  17. European Medicines Agency. Xofigo: summary of product characteristics. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002653/WC500156172.pdf. Accessed 24 Feb 2014.

  18. Heier-Baardson H, Dornish M. Lack of protective effect by hypoxia on alpha particle radiation from radium-223 [abstract no. 855]. EJC Suppl. 2010;8(5):216.

    Article  Google Scholar 

  19. Henriksen G, Fisher DR, Roeske JC, et al. Targeting of osseous sites with α-emitting 223Ra: comparison with the β-emitter 89Sr in mice. J Nucl Med. 2003;44(2):252–9.

    PubMed  CAS  Google Scholar 

  20. Nilsson S, Larsen RH, Fosså SD, et al. First clinical experience with α-emitting radium-223 in the treatment of skeletal metastases. Clin Cancer Res. 2005;11(12):4451–9.

    Article  PubMed  CAS  Google Scholar 

  21. Nilsson S, Franzén L, Parker C, et al. Bone-targeted radium-223 in symptomatic, hormone-refractory prostate cancer: a randomised, multicentre, placebo-controlled phase II study. Lancet Oncol. 2007;8(7):587–94.

    Article  PubMed  CAS  Google Scholar 

  22. Chittenden S, Hindorf C, Aksnes A, et al. Dosimetry and pharmacokinetics of 223Ra chloride in patients with bone metastases due to hormone refractory prostate cancer [abstract no. P0019]. Eur J Nucl Med Mol Imaging. 2012;39(2 Suppl):S308–9.

    Google Scholar 

  23. Lewington V, Parker C, Hindorf C, et al. Radium-223 chloride, a first-in-class alpha-pharmaceutical for patients with castration-resistant prostate cancer (CRPC) and bone metastases: biodistribution/dosimetry compared to overall safety profile [abstract no. e15009]. J Clin Oncol. 2010;28(15 Suppl).

  24. Carrasquillo JA, O’Donoghue JA, Pandit-Taskar N, et al. Phase I pharmacokinetic and biodistribution study with escalating doses of 223Ra-dichloride in men with castration-resistant metastatic prostate cancer. Eur J Nucl Med Mol Imaging. 2013;40(9):1384–93.

    Article  PubMed  CAS  Google Scholar 

  25. McDevitt MR, Sgouros G, Finn RD, et al. Radioimmunotherapy with alpha-emitting nuclides. Eur J Nucl Med. 1998;25(9):1341–51.

    Article  PubMed  CAS  Google Scholar 

  26. Bruland ØS, Nilsson S, Fisher DR, et al. High-linear energy transfer irradiation targeted to skeletal metastases by the α-emitter 223Ra: adjuvant or alternative to conventional modalities? Clin Cancer Res. 2006;12(20 Suppl):6250s–7s.

    Article  PubMed  CAS  Google Scholar 

  27. Franken NAP, Hovingh S, Ten Cate R, et al. Relative biological effectiveness of high linear energy transfer α-particles for the induction of DNA-double-strand breaks, chromosome aberrations and reproductive cell death in SW-1573 lung tumour cells. Oncol Rep. 2012;27(3):769–74.

    PubMed  CAS  Google Scholar 

  28. Baidoo KE, Yong K, Brechbiel MW. Molecular pathways: targeted α-particle radiation therapy. Clin Cancer Res. 2013;19(3):530–7.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  29. Lassmann M, Nosske D. Dosimetry of 223Ra-chloride: dose to normal organs and tissues. Eur J Nucl Med Mol Imaging. 2013;40(2):207–12.

    Article  PubMed  CAS  Google Scholar 

  30. Parker C, Nilsson S, Heinrich D, et al. Alpha emitter radium-223 and survival in metastatic prostate cancer. N Engl J Med. 2013;369(3):213–23.

    Article  PubMed  CAS  Google Scholar 

  31. Oken MM, Creech RH, Tormey DC, et al. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol. 1982;5(6):649–55.

    Article  PubMed  CAS  Google Scholar 

  32. Parker C, Heinrich D, O’Sullivan JM, et al. Overall survival benefit of radium-223 chloride (Alpharadin™) in the treatment of patients with symptomatic bone metastases in castration-resistant prostate cancer (CRPC): a phase III randomized trial (ALSYMPCA) [abstract no. 1LBA]. Eur J Cancer. 2011;47(Suppl 2):3.

    Article  Google Scholar 

  33. Vogelzang N, Parker C, Nilsson S, et al. Updated analysis of radium-223 dichloride impact on skeletal-related events (SRE) in patients with castration-resistant prostate cancer (CRPC) and bone metastases from the phase 3 randomized trial (ALSYMPCA) [abstract no. 11 plus poster]. J Clin Oncol. 2013;31(6 Suppl):11.

    Google Scholar 

  34. Parker C, O’Bryan-Tear CG, Bolstad B, et al. Alkaline phosphatase (ALP) normalization and overall survival in patients with bone metastases from castration-resistant prostate cancer (CRPC) treated with radium-223 [abstract no. 49]. J Clin Oncol. 2011;29(7 Suppl):49.

    Google Scholar 

  35. Nilsson S, Sartor AO, Bruland OS, et al. Pain analyses from the phase III randomized ALSYMPCA study with radium-223 dichloride (Ra-223) in castration-resistant prostate cancer (CRPC) patients with bone metastases [abstract no. 5038]. J Clin Oncol. 2013;31(15 Suppl):5038.

    Google Scholar 

  36. Tomblyn M, Nilsson S, Vogelzang N, et al. Pain and quality of life (QoL) analyses from the phase 3 randomized ALSYMPCA study with radium-223 dichloride (Ra-223) in castration-resistant prostate cancer (CRPC) patients with bone metastases [abstract no. 714]. J Urol. 2013;189(4 Suppl):e293.

    Article  Google Scholar 

  37. Esper P, Mo F, Chodak G, et al. Measuring quality of life in men with prostate cancer using the Functional Assessment of Cancer Therapy-Prostate instrument. Urology. 1997;50(6):920–8.

    Article  PubMed  CAS  Google Scholar 

  38. Parker CC, Pascoe S, Chodacki A, et al. 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. 2013;63(2):189–97.

    PubMed  CAS  Google Scholar 

  39. Edge SB, Byrd DR, Compton CC, et al., editors. AJCC Cancer Staging Manual. 7th ed. New York: Springer; 2010.

    Google Scholar 

  40. National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology (NCCN Guideline®): prostate cancer (Version 1.2014). 2014. http://www.nccn.org/professionals/physician_gls/pdf/prostate.pdf. Accessed 24 Feb 2014.

  41. Harrison MR, Wong TZ, Armstrong AJ, et al. Radium-223 chloride: a potential new treatment for castration-resistant prostate cancer patients with metastatic bone disease. Cancer Manag Res. 2013;5(1):1–14.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  42. Bayer. A re-treatment safety study of radium-223 dichloride in subjects with castration-resistant prostate cancer with bone metastases who received an initial course of six doses of radium-223 dichloride 50 kBq/kg every four weeks [ClinicalTrials.gov identifier: NCT01934790]. US National Institutes of Health, ClinicalTrials.gov (online). 2014. http://clinicaltrials.gov/ct2/show/NCT01934790?term=NCT01934790&rank=1. Accessed 24 Feb 2014.

  43. Bayer. A randomized open-label phase IIa study evaluating the efficacy and safety of radium-223 dichloride in combination with abiraterone acetate or enzalutamide in subjects with CRPC who have bone metastases [ClinicalTrials.gov identifier: NCT02034552]. US National Institutes of Health. ClinicalTrials.gov (online). 2014. http://clinicaltrials.gov/ct2/show/record/NCT02034552?term=NCT02034552&rank=1. Accessed 24 Feb 2014.

  44. Algeta ASA. A phase I/IIa study of safety and efficacy of Alpharadin® with docetaxel in patients with bone metastasis from castration-resistant prostate cancer [ClinicalTrials.gov identifier: NCT01106352]. US National Institutes of Health. ClinicalTrials.gov (online). 2014. http://clinicaltrials.gov/ct2/show/record/NCT01106352?term=NCT01106352&rank=1. Accessed 24 Feb 2014.

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Disclosure

The preparation of this review was not supported by any external funding. During the peer review process, the manufacturer of the agent under review was offered an opportunity to comment on this article. Changes resulting from comments received were made by the authors on the basis of scientific and editorial merit.

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  1. Adis, 41 Centorian Drive, Private Bag 65901, Mairangi Bay, North Shore, 0754, Auckland, New Zealand

    Matt Shirley & Paul L. McCormack

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  1. Matt Shirley
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Correspondence to Matt Shirley.

Additional information

The manuscript was reviewed by: J.B. Aragon-Ching, Department of Medicine, Division of Hematology/Oncology, George Washington University Medical Center, Washington, DC, USA; J. Carles, Department of Medical Oncology, Vall d’Hebron University Hospital, Barcelona, Spain; L. Costa, Hospital de Santa Maria and Instituto de Medicina Molecular, Lisbon, Portugal; D. Mukherji, Department of Internal Medicine, Division of Hematology/Oncology, American University of Beirut Medical Center, Beirut, Lebanon.

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Shirley, M., McCormack, P.L. Radium-223 Dichloride: A Review of Its Use in Patients with Castration-Resistant Prostate Cancer with Symptomatic Bone Metastases. Drugs 74, 579–586 (2014). https://doi.org/10.1007/s40265-014-0198-4

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