A randomized, dose-response, multicenter phase II study of radium-223 chloride for the palliation of painful bone metastases in patients with castration-resistant prostate cancer

Eur J Cancer. 2012 Mar;48(5):678-86. doi: 10.1016/j.ejca.2011.12.023. Epub 2012 Feb 15.

Abstract

Purpose: To investigate the dose-response relationship and pain-relieving effect of radium-223, a highly bone-targeted alpha-pharmaceutical.

Methods: One hundred patients with castration-resistant prostate cancer (CRPC) and painful bone metastases were randomized to a single intravenous dose of 5, 25, 50 or 100 k Bq/kg radium-223. The primary end-point was pain index (visual analogue scale [VAS] and analgesic use), also used to classify patients as responders or non-responders.

Results: A significant dose response for pain index was seen at week 2 (P = .035). At week 8 there were 40%, 63%, 56% and 71% pain responders (reduced pain and stable analgesic consumption) in the 5, 25, 50 and 100 k Bq/kg groups, respectively. On the daily VAS, at week 8, pain decreased by a mean of -30, -31, -27 and -28 mm, respectively (P = .008, P = .0005, P = .002, and P < . 0001) in these responders (post-hoc analysis). There was also a significant improvement in the brief pain inventory functional index for all dose-groups (P = .04, .01, .002 and .02, Wilcoxon signed rank test). Furthermore, a decrease in bone alkaline phosphatase in the highest dose-group was demonstrated (P = .0067). All doses were safe and well tolerated.

Conclusion: Pain response was seen in up to 71% of the patients with a dose response observed 2 weeks after administration. The highly tolerable side-effect profile of radium-223 previously reported was confirmed.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adenocarcinoma / complications
  • Adenocarcinoma / pathology
  • Adenocarcinoma / radiotherapy*
  • Adenocarcinoma / secondary
  • Aged
  • Bone Neoplasms / complications
  • Bone Neoplasms / pathology
  • Bone Neoplasms / radiotherapy*
  • Bone Neoplasms / secondary*
  • Dose-Response Relationship, Radiation
  • Double-Blind Method
  • Humans
  • Male
  • Pain / etiology
  • Pain / radiotherapy*
  • Palliative Care / methods*
  • Prostatic Neoplasms / complications
  • Prostatic Neoplasms / pathology*
  • Prostatic Neoplasms / radiotherapy*
  • Radium / therapeutic use*
  • Survival Analysis

Substances

  • Radium