What is the name of the alpha particle therapy currently in trials for older adults with castration-resistant prostate cancer that has metastasized to the bones?

Radium-223 for Castration-Resistant Prostate Cancer with Bone Metastases

The alpha particle therapy currently in trials and approved for older adults with castration-resistant prostate cancer metastasized to bones is Radium-223 dichloride (Xofigo). 1, 2

Mechanism and Characteristics

Radium-223 is an alpha-emitting radiopharmaceutical that selectively targets bone metastases by mimicking calcium and incorporating into newly formed bone stroma at metastatic sites. 1 The high-energy alpha particles have a short range (less than 100 micrometers), which allows them to:

• Induce double-strand DNA breaks in tumor cells, leading to cell death 1, 3
• Minimize damage to adjacent bone marrow and normal tissues due to the limited radiation path 1
• Disrupt the positive-feedback loops between tumor cells and the bone microenvironment 3

Survival and Clinical Benefits

Radium-223 is the first and only bone-targeting agent proven to extend overall survival in this population. 1 The pivotal ALSYMPCA trial demonstrated:

• Median overall survival improved from 11.3 months with placebo to 14.9 months with radium-223 (HR 0.70,95% CI 0.58-0.83, P<0.001) 1, 2
• Time to first skeletal-related event increased from 9.8 months to 15.6 months (HR 0.658,95% CI 0.522-0.830, P=0.00037) 1
• Significant improvements in quality of life measurements 1
• Benefits occurred regardless of prior docetaxel exposure 1

Patient Selection Criteria

Radium-223 is FDA-approved specifically for patients with castration-resistant prostate cancer, symptomatic bone metastases, and no known visceral metastatic disease. 2 Key eligibility requirements include:

• Symptomatic bone metastases requiring regular analgesics 1, 4
• Castrate testosterone levels maintained with ongoing androgen deprivation therapy 1, 2
• Absolute contraindication: presence of visceral metastases or malignant lymphadenopathy exceeding 3 cm 2
• Good performance status (ECOG 0-1) for standard recommendations 1, 4

Administration Protocol

The standard regimen is 55 kBq (1.49 microcurie) per kg body weight administered intravenously every 4 weeks for 6 cycles. 1, 2 Treatment is delivered by appropriately licensed facilities, typically in nuclear medicine or radiation therapy departments. 1

Hematologic Requirements and Monitoring

Prior to initial dose, patients must have: 1

• Absolute neutrophil count ≥ 1.5 × 10⁹/L
• Platelet count ≥ 100 × 10⁹/L
• Hemoglobin ≥ 10 g/dL

Prior to subsequent doses, patients must have: 1

• Absolute neutrophil count ≥ 1 × 10⁹/L
• Platelet count ≥ 50 × 10⁹/L (though this may be too low in clinical practice)

Discontinue radium-223 if blood counts do not recover within 6-8 weeks after treatment. 1, 2

Safety Profile

Radium-223 demonstrates remarkably low hematologic toxicity compared to beta-emitting radiopharmaceuticals: 1

• Grade 3-4 neutropenia: 2-3% 1
• Grade 3-4 thrombocytopenia: 3-6% 1
• Grade 3-4 anemia: 6-13% 1

Non-hematologic side effects are generally mild and include: 1

• Nausea, diarrhea, and vomiting (related to fecal excretion of the agent)
• These symptoms are manageable and do not typically require treatment discontinuation

Critical Contraindications and Restrictions

Do not combine radium-223 with docetaxel or other systemic chemotherapy (except androgen deprivation therapy) outside of clinical trials due to additive myelosuppression risk. 1 Preliminary data suggest combination with standard-dose docetaxel should not be undertaken. 1

WARNING: Do not combine radium-223 with abiraterone acetate plus prednisone/prednisolone without mandatory bone-protecting agents. 2 The ERA-223 trial was terminated early due to increased fracture rates (45.9% with combination vs 22.3% with enzalutamide alone at 1.5 years). 1, 4

Mandatory Bone Protection

All patients receiving radium-223 must be given concomitant denosumab or zoledronic acid throughout treatment to prevent pathological fractures. 4 This is now considered a mandatory safety requirement based on the ERA-223 trial findings. 1, 4 Concomitant use of these bone-protecting agents does not interfere with the survival benefits of radium-223. 1

Clinical Positioning

Radium-223 receives a Category 1 recommendation from NCCN as a first-line or second-line option for patients with symptomatic bone metastases and no visceral disease. 1 It represents an attractive first-line alternative for patients who are:

• Too frail to receive docetaxel chemotherapy 1
• Seeking treatment with a favorable toxicity profile 1, 5
• Requiring bone-targeted therapy with proven survival benefit 1

Common Pitfalls to Avoid

Never use radium-223 in patients with visceral metastases - this is an absolute FDA contraindication that excludes patients from treatment eligibility. 2

Never omit bone-protecting agents (denosumab or zoledronic acid) - fracture risk increases dramatically without mandatory bone protection, as demonstrated by the ERA-223 trial showing fracture rates of 45.9% without bone protection. 1, 4

Do not use in asymptomatic or minimally symptomatic patients - radium-223 is specifically indicated for symptomatic bone metastases requiring analgesics, not for asymptomatic disease. 1, 4

Avoid combining with secondary hormonal therapies outside clinical trials without bone protection - the combination with abiraterone or enzalutamide requires mandatory bone-protecting agents to prevent catastrophic fracture rates. 1, 4, 2