title: 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.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Oncology, Radiumhemmet, Karolinska Hospital, SE-171 76 Stockholm, Sweden. Sten.Nilsson@ki.se
authors.forename: S
authors.initials: S
authors.lastname: Nilsson
authors.forename: P
authors.initials: P
authors.lastname: Strang
authors.forename: A K
authors.initials: AK
authors.lastname: Aksnes
authors.forename: L
authors.initials: L
authors.lastname: Franzèn
authors.forename: P
authors.initials: P
authors.lastname: Olivier
authors.forename: A
authors.initials: A
authors.lastname: Pecking
authors.forename: J
authors.initials: J
authors.lastname: Staffurth
authors.forename: S
authors.initials: S
authors.lastname: Vasanthan
authors.forename: C
authors.initials: C
authors.lastname: Andersson
authors.forename: Ø S
authors.initials: ØS
authors.lastname: Bruland
mesh_terms: D000230:Adenocarcinoma / Q000150:complications / Q000473:pathology / Q000532:radiotherapy* / Q000556:secondary; D000368:Aged; D001859:Bone Neoplasms / Q000150:complications / Q000473:pathology / Q000532:radiotherapy* / Q000556:secondary*; D004307:Dose-Response Relationship, Radiation; D004311:Double-Blind Method; D006801:Humans; D008297:Male; D010146:Pain / Q000209:etiology / Q000532:radiotherapy*; D010166:Palliative Care / Q000379:methods*; D011471:Prostatic Neoplasms / Q000150:complications / Q000473:pathology* / Q000532:radiotherapy*; D011883:Radium / Q000627:therapeutic use*; D016019:Survival Analysis
chemical_list: D011883:Radium