PMID- 23000088
OWN - NLM
STAT- MEDLINE
DCOM- 20130708
LR  - 20211122
IS  - 1873-7560 (Electronic)
IS  - 0302-2838 (Linking)
VI  - 63
IP  - 2
DP  - 2013 Feb
TI  - A randomized, double-blind, dose-finding, multicenter, phase 2 study of radium 
      chloride (Ra 223) in patients with bone metastases and castration-resistant 
      prostate cancer.
PG  - 189-97
LID - S0302-2838(12)01031-7 [pii]
LID - 10.1016/j.eururo.2012.09.008 [doi]
AB  - BACKGROUND: Patients with castration-resistant prostate cancer (CRPC) and bone 
      metastases have an unmet clinical need for effective treatments that improve 
      quality of life and survival with a favorable safety profile. OBJECTIVE: To 
      prospectively evaluate the efficacy and safety of three different doses of radium 
      chloride (Ra 223) in patients with CRPC and bone metastases. DESIGN, SETTING, AND 
      PARTICIPANTS: In this phase 2 double-blind multicenter study, 122 patients were 
      randomized to receive three injections of Ra 223 at 6-wk intervals, at doses of 
      25 kBq/kg (n=41), 50 kBq/kg (n=39), or 80 kBq/kg (n=42). The study compared the 
      proportion of patients in each dose group who had a confirmed decrease of >/= 50% 
      in baseline prostate-specific antigen (PSA) levels. OUTCOME MEASUREMENTS AND 
      STATISTICAL ANALYSIS: Efficacy was evaluated using blood samples to measure PSA 
      and other tumor markers, recorded skeletal-related events, and pain assessments. 
      Safety was evaluated using adverse events (AEs), physical examination, and 
      clinical laboratory tests. The Jonckheere-Terpstra test assessed trends between 
      groups. RESULTS AND LIMITATIONS: The study met its primary end point with a 
      statistically significant dose-response relationship in confirmed >/= 50% PSA 
      declines for no patients (0%) in the 25-kBq/kg dose group, two patients (6%) in 
      the 50-kBq/kg dose group, and five patients (13%) in the 80-kBq/kg dose group 
      (p=0.0297). A >/= 50% decrease in bone alkaline phosphatase levels was identified 
      in six patients (16%), 24 patients (67%), and 25 patients (66%) in the 25-, 50-, 
      and 80-kBq/kg dose groups, respectively (p<0.0001). The most common 
      treatment-related AEs (>/= 10%) occurring up to week 24 across all dose groups were 
      diarrhea (21%), nausea (16%), and anemia (14%). No difference in incidence of 
      hematologic events was seen among dose groups. Potential limitations include 
      small patient numbers and differences among dose groups at baseline. CONCLUSIONS: 
      Ra 223 had a dose-dependent effect on serum markers of CRPC activity, suggesting 
      that control of bone disease with Ra 223 may affect cancer-related outcomes. Ra 
      223 was well tolerated at all doses. TRIAL REGISTRATION: ClinicalTrials.gov: 
      NCT00337155.
CI  - Copyright (c) 2012 European Association of Urology. Published by Elsevier B.V. All 
      rights reserved.
FAU - Parker, Christopher C
AU  - Parker CC
AD  - Royal Marsden Hospital, Sutton, UK. chris.parker@rmh.nhs.uk
FAU - Pascoe, Sarah
AU  - Pascoe S
FAU - Chodacki, Ales
AU  - Chodacki A
FAU - O'Sullivan, Joe M
AU  - O'Sullivan JM
FAU - Germa, Josep R
AU  - Germa JR
FAU - O'Bryan-Tear, Charles Gillies
AU  - O'Bryan-Tear CG
FAU - Haider, Trond
AU  - Haider T
FAU - Hoskin, Peter
AU  - Hoskin P
LA  - eng
SI  - ClinicalTrials.gov/NCT00337155
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
DEP - 20120913
PL  - Switzerland
TA  - Eur Urol
JT  - European urology
JID - 7512719
RN  - 0 (Radioisotopes)
RN  - 0 (Radiopharmaceuticals)
RN  - EC 3.1.3.1 (Alkaline Phosphatase)
RN  - EC 3.4.21.- (KLK3 protein, human)
RN  - EC 3.4.21.- (Kallikreins)
RN  - EC 3.4.21.77 (Prostate-Specific Antigen)
RN  - RJ00KV3VTG (radium Ra 223 dichloride)
RN  - W90AYD6R3Q (Radium)
SB  - IM
CIN - Eur Urol. 2013 Feb;63(2):198-200. PMID: 23062225
MH  - Adenocarcinoma/blood/*radiotherapy/secondary
MH  - Aged
MH  - Alkaline Phosphatase/blood
MH  - Alpha Particles/*therapeutic use
MH  - Bone Neoplasms/blood/*radiotherapy/secondary
MH  - Dose-Response Relationship, Radiation
MH  - Double-Blind Method
MH  - Drug Administration Schedule
MH  - Humans
MH  - Kallikreins/*blood
MH  - Male
MH  - Middle Aged
MH  - Pain Measurement
MH  - Prospective Studies
MH  - Prostate-Specific Antigen/*blood
MH  - Prostatic Neoplasms/pathology/*radiotherapy
MH  - Radioisotopes/administration & dosage
MH  - Radiopharmaceuticals/*administration & dosage
MH  - Radium/*administration & dosage
MH  - Treatment Outcome
EDAT- 2012/09/25 06:00
MHDA- 2013/07/09 06:00
CRDT- 2012/09/25 06:00
PHST- 2012/04/20 00:00 [received]
PHST- 2012/09/03 00:00 [accepted]
PHST- 2012/09/25 06:00 [entrez]
PHST- 2012/09/25 06:00 [pubmed]
PHST- 2013/07/09 06:00 [medline]
AID - S0302-2838(12)01031-7 [pii]
AID - 10.1016/j.eururo.2012.09.008 [doi]
PST - ppublish
SO  - Eur Urol. 2013 Feb;63(2):189-97. doi: 10.1016/j.eururo.2012.09.008. Epub 2012 Sep 
      13.