Bone-targeted radium-223 in symptomatic, hormone-refractory prostate cancer: a randomised, multicentre, placebo-controlled phase II study

Lancet Oncol. 2007 Jul;8(7):587-94. doi: 10.1016/S1470-2045(07)70147-X.


Background: The alpha-emitter radium-223 ((223)Ra) is a bone-seeking radionuclide studied as a new treatment for patients with bone metastases from hormone-refractory prostate cancer. We aimed to study mature outcomes from a randomised, multicentre, phase II study of (223)Ra.

Methods: Patients with hormone-refractory prostate cancer and bone pain needing external-beam radiotherapy were assigned to four intravenous injections of (223)Ra (50 kBq/kg, 33 patients) or placebo (31 patients), given every 4 weeks. Primary endpoints were change in bone-alkaline phosphatase (ALP) concentration and time to skeletal-related events (SREs). Secondary endpoints included toxic effects, time to prostate-specific-antigen (PSA) progression, and overall survival. All tests were done at a 5% significance level, based on intention to treat.

Findings: Median relative change in bone-ALP during treatment was -65.6% (95% CI -69.5 to -57.7) and 9.3% (3.8-60.9) in the (223)Ra group and placebo groups, respectively (p<0.0001, Wilcoxon ranked-sums test). Hazard ratio for time to first SRE, adjusted for baseline covariates, was 1.75 (0.96-3.19, p=0.065, Cox regression). Haematological toxic effects did not differ significantly between two groups. No patient discontinued (223)Ra because of treatment toxicity. Median time to PSA progression was 26 weeks (16-39) versus 8 weeks (4-12; p=0.048) for (223)Ra versus placebo, respectively. Median overall survival was 65.3 weeks (48.7-infinity) for (223)Ra and 46.4 weeks (32.1-77.4) for placebo (p=0.066, log rank). The hazard ratio for overall survival, adjusted for baseline covariates was 2.12 (1.13-3.98, p=0.020, Cox regression).

Interpretation: (223)Ra was well tolerated with minimum myelotoxicity, and had a significant effect on bone-ALP concentrations. Larger clinical trials are warranted to study (223)Ra on the prevention of SREs and on overall survival in patients with hormone-refractory prostate cancer. Bone-targeting properties of (223)Ra could also potentially be used for treating skeletal metastasis from other primary cancers.

Publication types

  • Clinical Trial, Phase II
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adenocarcinoma / radiotherapy
  • Adenocarcinoma / secondary
  • Aged
  • Aged, 80 and over
  • Alkaline Phosphatase / blood
  • Bone Neoplasms / radiotherapy*
  • Bone Neoplasms / secondary
  • Double-Blind Method
  • Drug Resistance, Neoplasm*
  • Humans
  • Male
  • Middle Aged
  • Placebos
  • Prognosis
  • Prostate-Specific Antigen
  • Prostatic Neoplasms / pathology
  • Prostatic Neoplasms / radiotherapy*
  • Radium / therapeutic use*
  • Survival Rate


  • Placebos
  • Alkaline Phosphatase
  • Prostate-Specific Antigen
  • Radium