Radium-223 for the treatment of bone metastases in castration-resistant prostate cancer: when and why

Abstract

Radium-223 dichloride (223Ra) is the first, recently approved, α-particle-emitting radiopharmaceutical for the treatment of patients with bone metastases in castration-resistant prostate cancer (CRPC) and no evidence of visceral metastases. We explored MEDLINE, relevant congresses, and websites for data on 223Ra and prostate cancer therapies, focusing on therapeutic strategies and timing, bone metastases, and diagnostic assessment. 223Ra represents the only bone-targeting agent that has significantly extended patients’ overall survival while reducing pain and symptomatic skeletal events. Unlike other radiopharmaceuticals, such as strontium-89 and samarium-153 EDTMP, 223Ra (11.4-days half-life) has shown a high biological efficiency mainly due to its short penetration range. These features potentially allow reduced bone marrow toxicity and limit undue exposure. 223Ra has been validated under the product name Xofigo® by the US Food and Drug Administration and the European Medicines Agency. Patient selection, management, and treatment sequencing is recommended to be discussed in the context of a multidisciplinary environment, including oncology, urology, nuclear medicine, and radiation therapy physicians. No consensus has been achieved regarding the optimal timing and its administration as single agent or in combination with zoledronic acid or chemotherapy, so far. This review aims to provide a rationale for the use of 223Ra in treating metastases from CRPC, highlighting the crucial role of a multidisciplinary approach, the disputed inclusion and exclusion criteria on the basis of agencies regulations, and the value of diagnostics for therapy assessment.

Osteoimmuno-Oncology: Therapeutic Opportunities for Targeting Immune Cells in Bone Metastasis

“…Radium-223 dichloride is approved for the treatment of CRPC patients with bone metastases [ 188 ]. As a calcium mimetic, radium-223 dichloride accumulates in bone, especially in high turnover states such as in cancer bone metastasis [ 188 ].…”

α‐Emitting cancer therapy using 211At‐AAMT targeting LAT1

“…Targeted α‐therapy (TAT) is the selective delivery of α‐emitters to tumors using high linear energy transfer (LET) α‐particles, while minimizing damage to surrounding tissues 2 . Radium‐223 ( 223 Ra) dichloride has been used as a treatment for bone metastasis (ie, Xofigo®), as well as for pain management 3,4 . Actinium‐225 ( 225 Ac)‐PSMA‐617 has been shown to have significant benefits for patients with advanced‐stage or chemo‐naïve prostate cancer 5‐10 .…”

“…2 Radium-223 ( 223 Ra) dichloride has been used as a treatment for bone metastasis (ie, Xofigo®), as well as for pain management. 3,4 Actinium-225 ( 225 Ac)-PSMA-617 has been shown to have significant benefits for patients with advanced-stage or chemo-naïve prostate cancer. [5][6][7][8][9][10] Radiopharmaceuticals are practical and effective treatment, albeit with their restrictions.…”

A real-world evaluation of radium-223 in combination with abiraterone or enzalutamide for the treatment of metastatic castration-resistant prostate cancer

“…Less than 2% of the entire cohort of patients in the ERA 223 trial had previous use of docetaxel (all in the hormone sensitive setting), compared to 57% in the ALSYMPCA trial, and 32% in the present study. Optimal timing of radium-223 in the disease course has been proposed as prior to chemotherapy, when performance status is preserved, and before skeletal involvement is widespread, as the bone marrow reserve is still spared [ 15 ].…”