title: Two-year survival follow-up of the randomized, double-blind, placebo-controlled phase II study of radium-223 chloride in patients with castration-resistant prostate cancer and bone metastases.
abstract: BACKGROUND
  This phase II randomized, placebo-controlled study was conducted to evaluate efficacy and safety of radium-223 in patients with castration-resistant prostate cancer (CRPC) and painful bone metastases. Twelve- and 18-month survival results were reported previously. Here we report 24-month overall survival (OS) and safety data from the period 12 to 24 months after the first injection of study medication.
  
  
  METHODS
  Patients with CRPC and bone pain were randomized 1:1 to receive 4 injections of radium-223 (50 kBq/kg [n = 33]) or placebo (n = 31) after external-beam radiotherapy; each injection was given every 4 weeks. Endpoints for this report were 24-month OS, long-term safety, and treatment-related adverse events (AEs) occurring in the 12- to 24-month period.
  
  
  RESULTS
  After 24 months, 10 (30%) patients were alive in the radium-223 group compared with 4 patients (13%) in the placebo group. Patients who received at least 1 dose of study medication had a median OS of 65 weeks in the radium-223 group vs. 46 weeks in the placebo group (log-rank P = .056). The hazard ratio (HR) for OS, adjusted for baseline covariates, was 0.476 (95% confidence interval [CI], 0.258-0.877; Cox regression P = .017). The most frequent cause of death for both arms was disease progression. There were no reports of treatment-related AEs or long-term hematologic toxicity during the 12- to 24-month follow-up.
  
  
  CONCLUSIONS
  Radium-223 had a highly favorable safety profile, with no evidence of second malignancies at 24-month follow-up. The significant improvement in OS observed in patients receiving radium-223 vs. placebo suggests that treatment of bone disease with radium-223 has survival benefits.
authors.affiliation: Karolinska University Hospital, Stockholm, Sweden. sten.nilsson@ki.se
authors.forename: Sten
authors.initials: S
authors.lastname: Nilsson
authors.forename: Lars
authors.initials: L
authors.lastname: Franzén
authors.forename: Christopher
authors.initials: C
authors.lastname: Parker
authors.forename: Christopher
authors.initials: C
authors.lastname: Tyrrell
authors.forename: René
authors.initials: R
authors.lastname: Blom
authors.forename: Jan
authors.initials: J
authors.lastname: Tennvall
authors.forename: Bo
authors.initials: B
authors.lastname: Lennernäs
authors.forename: Ulf
authors.initials: U
authors.lastname: Petersson
authors.forename: Dag C
authors.initials: DC
authors.lastname: Johannessen
authors.forename: Michael
authors.initials: M
authors.lastname: Sokal
authors.forename: Katharine
authors.initials: K
authors.lastname: Pigott
authors.forename: Charles Gillies
authors.initials: CG
authors.lastname: O'Bryan-Tear
authors.forename: Marcus
authors.initials: M
authors.lastname: Thuresson
authors.forename: Bjørg
authors.initials: B
authors.lastname: Bolstad
authors.forename: Øyvind S
authors.initials: ØS
authors.lastname: Bruland
mesh_terms: D000230:Adenocarcinoma / Q000401:mortality / Q000532:radiotherapy* / Q000556:secondary; D000368:Aged; D000369:Aged, 80 and over; D001859:Bone Neoplasms / Q000401:mortality / Q000532:radiotherapy* / Q000556:secondary; D017322:Clinical Trials, Phase II as Topic; D003131:Combined Modality Therapy; D000077143:Docetaxel; D004311:Double-Blind Method; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D059408:Pain Management; D010166:Palliative Care; D016016:Proportional Hazards Models; D011471:Prostatic Neoplasms / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D011868:Radioisotopes / Q000008:administration & dosage; D019275:Radiopharmaceuticals / Q000008:administration & dosage*; D011883:Radium / Q000008:administration & dosage*; D016032:Randomized Controlled Trials as Topic; D043823:Taxoids / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D011868:Radioisotopes; D019275:Radiopharmaceuticals; D043823:Taxoids; D000077143:Docetaxel; C581106:radium Ra 223 dichloride; D011883:Radium