Radiation safety considerations for the use of ²²³RaCl₂ DE in men with castration-resistant prostate cancer

Health Phys. 2014 Apr;106(4):494-504. doi: 10.1097/HP.0b013e3182a82b37.

Abstract

The majority of patients with late stage castration-resistant prostate cancer (CRPC) develop bone metastases that often result in significant bone pain. Therapeutic palliation strategies can delay or prevent skeletal complications and may prolong survival. An alpha-particle based therapy, radium-223 dichloride (²²³RaCl₂), has been developed that delivers highly localized effects in target areas and likely reduces toxicity to adjacent healthy tissue, particularly bone marrow. Radiation safety aspects were evaluated for a single comprehensive cancer center clinical phase 1, open-label, single ascending-dose study for three cohorts at 50, 100, or 200 kBq kg⁻¹ body weight. Ten patients received administrations, and six patients completed the study with 1 y follow-up. Dose rates from patients administered ²²³Ra dichloride were typically less than 2 μSv h⁻¹ MBq⁻¹ on contact and averaged 0.02 μSv h⁻¹ MBq⁻¹ at 1 m immediately following administration. Removal was primarily by fecal excretion, and whole body effective half-lives were highly dependent upon fecal compartment transfer, ranging from 2.5-11.4 d. Radium-223 is safe and straightforward to administer using conventional nuclear medicine equipment. For this clinical study, few radiation protection limitations were recommended post-therapy based on facility evaluations. Specific precautions are dependent on local regulatory authority guidance. Subsequent studies have demonstrated significantly improved overall survival and very low toxicity, suggesting that ²²³Ra may provide a new standard of care for patients with CRPC and bone metastases.

Publication types

  • Clinical Trial, Phase I
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alpha Particles
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Body Weight
  • Bone Neoplasms / prevention & control
  • Bone Neoplasms / secondary
  • Bone and Bones / pathology
  • Chlorides / chemistry
  • Dose-Response Relationship, Radiation
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Prostatic Neoplasms, Castration-Resistant / radiotherapy*
  • Radiation Protection / methods*
  • Radioisotopes / adverse effects
  • Radioisotopes / therapeutic use
  • Radiopharmaceuticals / adverse effects
  • Radiopharmaceuticals / therapeutic use*
  • Radium / adverse effects
  • Radium / therapeutic use*
  • Time Factors
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Chlorides
  • Radioisotopes
  • Radiopharmaceuticals
  • radium Ra 223 dichloride
  • Radium