Xofigo
Xofigo
Generic Name
Xofigo
Mechanism
- Radial mimicry of calcium: Radium‑223 substitutes for calcium at bone‑mineralization sites, concentrating in osteoblastic lesions.
- High‑energy α‑particles: Emit two ~5.5 MeV α‑particles that induce double‑strand DNA breaks within a 10–100 µm radius, selectively killing tumor cells adjacent to bone lesions.
- Limited systemic toxicity: α‑emission delivers localized dose; only ~1% of the emitted energy escapes beyond the tumour micro‑environment, resulting in minimal marrow exposure.
Pharmacokinetics
| Parameter | Typical Value | Comments |
| Absorption | IV infusion, 0.14 MBq/kg | Rapid systemic distribution. |
| Distribution | Whole‑body, preferentially bone | 31–58 % of injected dose localizes in bone. |
| Metabolism | Not metabolized; hydrolyzed after bone clearance | N/A |
| Elimination | Renal (≈50 %) and hepatic (≈30 %) | Excretion as chemically unchanged radium. |
| Half‑life | ~10 days (physical half‑life 11.4 days) | Consistent with 4‑weekly dosing cycle. |
| Bioavailability | 100 % | IV route eliminates first‑pass effects. |
> Key terms: α‑emitter, oligo‑detection, radiopharmaceutical.
Indications
- Bone‑predominant metastatic castration‑resistant prostate cancer in men who have progressed after endocrine or chemotherapy.
- Adds survival benefit when combined with standard care; improves overall survival and delays skeletal‑related events (SREs).
Contraindications
- Severe renal impairment (CrCl 3 bone‑marrow‑competing cytotoxic therapies**: avoid due to additive marrow toxicity.
Dosing
- Dosage: 55 kBq/kg IV over 3–5 minutes.
- Schedule: 4 injections at 4‑week intervals, for a total of 4 doses.
- Pre‑medication: Not required, but anti‑emetics can be used if nausea occurs.
- Infusion precautions: Ensure sterile technique; monitor for hypersensitivity.
> Tip: Baseline CBC and comprehensive metabolic panel are mandatory prior to the first dose.
Monitoring
| Parameter | Frequency | Thresholds |
| CBC (Hematology) | Schedule 2 and 4 weeks post‑dose | ANC < 1.0 × 10⁹/L or platelets < 100 × 10⁹/L |
| Creatinine (Kidney) | Baseline, then before each infusion | eGFR 3× ULN |
| PSA & alkaline phosphatase | At each visit | Track trends for disease burden |
| SRE events | Clinical assessment | Incidence reduction is key endpoint |
Clinical Pearls
- “Bone‑specific therapy”: Radium‑223 delivers radiation only to osteoblastic lesions, sparing rest of the body – ideal when chemotherapy is contraindicated.
- Combo synergy: Adding Docetaxel or Cabazitaxel after radium‑223 can be beneficial, but monitor marrow closely to avoid cumulative myelosuppression.
- Dose‑adjustment cues: If ANC < 1.5 × 10⁹/L or platelets < 100 × 10⁹/L after infusion, extend interval to 6 weeks or consider dose reduction.
- Radiation safety: Patients must avoid contact with infants/children for at least 14 days post‑infusion due to potential bone deposits; recommend wearing a mask during close interaction.
- Serologic markers: A rise in bone‑specific alkaline phosphatase within 4–6 weeks post‑therapy often indicates therapeutic response better than PSA changes alone.
- Safety margin: Even though α‑particles have short tracks, radium‑223 can accumulate in bone marrow over 4 cycles; thus, baseline DEXA or bone‑density imaging not routinely required, but caution if concurrent bisphosphonate therapy is used.
Search‑friendly keywords: radium‑223, Xofigo, bone‑mediated SREs, castration‑resistant prostate cancer, radiopharmaceutical therapy, alpha‑particle radiation.