²²³Ra-dichloride

Quick Answer

²²³Ra-dichloride is a calcium-mimetic alpha emitter that concentrates in areas of high bone turnover, delivering short-range, high-energy alpha radiation to osteoblastic bone metastases while largely sparing marrow. It is given as 55 kBq/kg IV every 4 weeks for 6 injections to men with mCRPC and symptomatic bone metastases and no known visceral metastatic disease. It improved overall survival in the ALSYMPCA trial.

The essentials in one place

²²³Ra-dichloride (Xofigo) is a calcium-mimetic alpha emitter for mCRPC with symptomatic bone metastases and no known visceral disease — a bone-microenvironment therapy that does not treat nodal/visceral disease. Dosing is 55 kBq/kg IV every 4 weeks × 6; ALSYMPCA showed an overall-survival benefit and delayed skeletal events. Do not combine with abiraterone + prednisone (ERA-223: more fractures and deaths) and ensure a bone-health agent. PSA is unreliable — follow alkaline phosphatase and clinical/skeletal endpoints, and never discontinue on PSA alone.

Clinical Importance

Ra-223 was the first alpha-emitting therapy to demonstrate an overall-survival benefit in a randomized trial and remains the standard radionuclide option for bone-dominant, symptomatic mCRPC. Its very short alpha range concentrates dose at the bone–tumor interface with relatively favorable marrow tolerance.

Evidence & Indication

• ALSYMPCA (2013): in mCRPC with symptomatic bone metastases and no known visceral disease, Ra-223 improved overall survival and delayed symptomatic skeletal events versus placebo.
• Indication: mCRPC with symptomatic bone metastases and no known visceral metastatic disease. It is a bone-microenvironment therapy — it does not treat visceral or nodal disease.

Patient Selection

• mCRPC with symptomatic bone metastases; no visceral metastases (small nodes may be acceptable per criteria).
• Adequate marrow reserve.
• Do not combine with abiraterone plus prednisone/prednisolone: the ERA-223 trial showed increased fractures and deaths with that combination. Ensure bone-health agents (e.g. denosumab/bisphosphonate) and fracture-risk assessment.

Preparation

Baseline CBC and confirmation of bone-dominant disease. Assess and optimize bone health.

Workflow

Confirm eligibility → check counts before each injection → slow IV bolus administration → repeat every 4 weeks for up to 6 injections.

Dose

55 kBq/kg body weight IV, every 4 weeks, for 6 injections. (Historical labeling used 50 kBq/kg under an older calibration standard; current standard is 55 kBq/kg — verify local convention.)

Monitoring

CBC before each dose (hemoglobin, neutrophils, platelets) with defined thresholds to proceed. Monitor for GI symptoms.

Radiation Safety

Alpha particles do not penetrate skin, so external exposure risk to others is minimal; the main precautions concern body fluids (Ra-223 is largely excreted in feces). Standard hygiene instructions apply.

Expected Outcomes

Overall-survival benefit, delayed symptomatic skeletal events, and pain improvement in appropriately selected patients. Note that PSA is not a reliable response marker for Ra-223 (it primarily targets the bone microenvironment); alkaline phosphatase trends and clinical/skeletal endpoints are more informative.

Complications & Toxicities

• Myelosuppression (anemia, thrombocytopenia, neutropenia).
• GI effects — nausea, diarrhea.
• Increased fracture risk when combined with abiraterone/prednisone (avoid that combination).

Monitoring & Holding Rules

Counts are checked before every injection with defined thresholds to proceed (e.g. hold for hemoglobin, neutrophil, or platelet levels below protocol cutoffs); persistent cytopenia leads to discontinuation. Because Ra-223 targets the bone microenvironment, treatment continues for the planned six injections unless toxicity or unequivocal clinical/radiographic progression intervenes.

Sequencing & Combinations

• Avoid concurrent abiraterone + prednisone/prednisolone — ERA-223 showed increased fractures and deaths with that combination; ensure a bone-health agent (denosumab or a bisphosphonate) and fracture-risk assessment.
• Ra-223 does not treat visceral or nodal disease — for those, systemic therapy (ARPI, taxane) or PSMA radioligand therapy is needed. Sequencing Ra-223 with Lu-177-PSMA (both bone-active/marrow-affecting) requires attention to cumulative marrow dose.
• Best suited to bone-dominant, symptomatic mCRPC without visceral metastases.

Response Assessment

Clinical (pain, skeletal events), alkaline phosphatase trend, and imaging. PSA is unreliable for Ra-223 — it may rise despite benefit because the alpha dose is deposited at the bone–tumor interface rather than throughout soft-tissue disease. Do not discontinue on PSA alone.

Self-Check

Key References

• Parker C, et al. Alpha emitter radium-223 and survival in metastatic prostate cancer (ALSYMPCA). N Engl J Med. 2013;369:213–223.
• Smith M, et al. ERA-223: addition of radium-223 to abiraterone/prednisone. Lancet Oncol. 2019.
• Xofigo prescribing information.