PMID- 28705540
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220412
IS  - 1873-7560 (Electronic)
IS  - 0302-2838 (Linking)
VI  - 73
IP  - 3
DP  - 2018 Mar
TI  - Three-year Safety of Radium-223 Dichloride in Patients with Castration-resistant 
      Prostate Cancer and Symptomatic Bone Metastases from Phase 3 Randomized 
      Alpharadin in Symptomatic Prostate Cancer Trial.
PG  - 427-435
LID - S0302-2838(17)30516-X [pii]
LID - 10.1016/j.eururo.2017.06.021 [doi]
AB  - BACKGROUND: In Alpharadin in Symptomatic Prostate Cancer (ALSYMPCA) trial, 
      radium-223 versus placebo prolonged overall survival with favorable safety in 
      castration-resistant prostate cancer patients with symptomatic bone metastases. 
      Long-term radium-223 monitoring underlies a comprehensive safety and risk/benefit 
      assessment. OBJECTIVE: To report updated ALSYMPCA safety, including long-term 
      safety up to 3 yr after the first injection. DESIGN, SETTING, AND PARTICIPANTS: 
      Safety analyses from phase 3 randomized ALSYMPCA trial included patients 
      receiving >/=1 study-drug injection (600 radium-223 and 301 placebo). Patients (405 
      radium-223 and 167 placebo) entered long-term safety follow-up starting 12 wk 
      after the last study-drug injection, to 3 yr from the first injection. 
      Forty-eight of 405 (12%) radium-223 and 12/167 (7%) placebo patients completed 
      follow-up, with evaluations every 2 mo for 6 mo, then every 4 mo until 3 yr. 
      OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: All adverse events (AEs) were 
      collected until 12 wk after the last injection; subsequently, only 
      treatment-related AEs were collected. Additional long-term safety was assessed by 
      development of acute myelogenous leukemia (AML), myelodysplastic syndrome (MDS), 
      aplastic anemia, and secondary malignancies. Data analysis used descriptive 
      statistics. RESULTS AND LIMITATIONS: During treatment to 12 wk following the last 
      injection, 564/600 (94%) radium-223 and 292/301 (97%) placebo patients had 
      treatment-emergent AEs (TEAEs). Myelosuppression incidence was low. Grade 3/4 
      hematologic TEAEs in radium-223 and placebo groups were anemia (13% vs 13%), 
      neutropenia (2% vs 1%), and thrombocytopenia (7% vs 2%). Ninety-eight of 600 
      (16%) radium-223 and 68/301 (23%) placebo patients experienced grade 5 TEAEs. 
      Long-term follow-up showed no AML, MDS, or new primary bone cancer; secondary 
      non-treatment-related malignancies occurred in four radium-223 and three placebo 
      patients. One radium-223 patient had aplastic anemia 16 mo after the last 
      injection. No other cases were observed. Limitations include short (3-yr) 
      follow-up. CONCLUSIONS: Final long-term safety ALSYMPCA analysis shows that 
      radium-223 remained well tolerated, with low myelosuppression incidence and no 
      new safety concerns. PATIENT SUMMARY: Updated Alpharadin in Symptomatic Prostate 
      Cancer (ALSYMPCA) trial findings show that radium-223 remained well tolerated 
      during treatment and up to 3 yr after each patient's first injection.
CI  - Copyright (c) 2017 European Association of Urology. Published by Elsevier B.V. All 
      rights reserved.
FAU - Parker, Christopher C
AU  - Parker CC
AD  - The Royal Marsden NHS Foundation Trust and Institute of Cancer Research, Sutton, 
      UK. Electronic address: chris.parker@rmh.nhs.uk.
FAU - Coleman, Robert E
AU  - Coleman RE
AD  - University of Sheffield, Weston Park Hospital, Sheffield, UK.
FAU - Sartor, Oliver
AU  - Sartor O
AD  - Tulane Cancer Center, New Orleans, LA, USA.
FAU - Vogelzang, Nicholas J
AU  - Vogelzang NJ
AD  - Comprehensive Cancer Centers of Nevada, Las Vegas, NV, USA.
FAU - Bottomley, David
AU  - Bottomley D
AD  - St James's University Hospital, Leeds, UK.
FAU - Heinrich, Daniel
AU  - Heinrich D
AD  - Akershus University Hospital, Lorenskog, Norway.
FAU - Helle, Svein I
AU  - Helle SI
AD  - Haukeland University Hospital, Bergen, Norway.
FAU - O'Sullivan, Joe M
AU  - O'Sullivan JM
AD  - Centre for Cancer Research and Cell Biology, Queen's University, Belfast, UK.
FAU - Fossa, Sophie D
AU  - Fossa SD
AD  - Radiumhospitalet, Oslo, Norway.
FAU - Chodacki, Ales
AU  - Chodacki A
AD  - Hospital Kochova, Chomutov, Czech Republic.
FAU - Wiechno, Pawel
AU  - Wiechno P
AD  - Centrum Onkologii-Instytut im Sklodowskiej-Curie, Warsaw, Poland.
FAU - Logue, John
AU  - Logue J
AD  - Christie Hospital, Manchester, UK.
FAU - Seke, Mihalj
AU  - Seke M
AD  - Centrallasarettet Vaxjo, Vaxjo, Sweden.
FAU - Widmark, Anders
AU  - Widmark A
AD  - Umea University, Umea, Sweden.
FAU - Johannessen, Dag Clement
AU  - Johannessen DC
AD  - Ulleval University Hospital, Oslo, Norway.
FAU - Hoskin, Peter
AU  - Hoskin P
AD  - Mount Vernon Hospital Cancer Centre, Middlesex, UK.
FAU - James, Nicholas D
AU  - James ND
AD  - Cancer Centre, University Hospitals Birmingham NHS Trust, Birmingham, UK.
FAU - Solberg, Arne
AU  - Solberg A
AD  - St Olavs Hospital, Trondheim, Norway.
FAU - Syndikus, Isabel
AU  - Syndikus I
AD  - Clatterbridge Center for Oncology, Wirral, UK.
FAU - Kliment, Jan
AU  - Kliment J
AD  - Jessenius School of Medicine, Comenius University, University Hospital, Martin, 
      Slovakia.
FAU - Wedel, Steffen
AU  - Wedel S
AD  - Department of Urology, Marien Hospital Herne, Ruhr-University Bochum, Herne, 
      Germany.
FAU - Boehmer, Sibylle
AU  - Boehmer S
AD  - Gemeinschaftspraxis, Berlin, Germany.
FAU - Dall'Oglio, Marcos
AU  - Dall'Oglio M
AD  - Hospital das Clinicas, Faculdade de Medicina da USP, Instituto do Cancer do 
      Estado de Sao Paulo, Brazil.
FAU - Franzen, Lars
AU  - Franzen L
AD  - Lanssjukhuset Sundsvall-Harnosand County Hospital, Sundsvall, Sweden; Umea 
      University Hospital, Umea, Sweden.
FAU - Bruland, Oyvind S
AU  - Bruland OS
AD  - Norwegian Radium Hospital Oslo, Norway; Faculty of Medicine, University of Oslo, 
      Oslo, Norway.
FAU - Petrenciuc, Oana
AU  - Petrenciuc O
AD  - Bayer HealthCare Pharmaceuticals, Whippany, NJ, USA.
FAU - Staudacher, Karin
AU  - Staudacher K
AD  - Bayer AS (formerly Algeta ASA), Oslo, Norway.
FAU - Li, Rui
AU  - Li R
AD  - Bayer HealthCare Pharmaceuticals, Whippany, NJ, USA.
FAU - Nilsson, Sten
AU  - Nilsson S
AD  - Karolinska University Hospital, Stockholm, Sweden.
LA  - eng
PT  - Journal Article
DEP - 20170711
PL  - Switzerland
TA  - Eur Urol
JT  - European urology
JID - 7512719
SB  - IM
CIN - Transl Androl Urol. 2018 Mar;7(Suppl 1):S132-S134. PMID: 29644181
OTO - NOTNLM
OT  - ALSYMPCA
OT  - Bone metastases
OT  - Castration-resistant prostate cancer
OT  - Follow-up
OT  - Long-term safety
OT  - Radium-223
EDAT- 2017/07/15 06:00
MHDA- 2017/07/15 06:01
CRDT- 2017/07/15 06:00
PHST- 2017/02/16 00:00 [received]
PHST- 2017/06/13 00:00 [accepted]
PHST- 2017/07/15 06:00 [pubmed]
PHST- 2017/07/15 06:01 [medline]
PHST- 2017/07/15 06:00 [entrez]
AID - S0302-2838(17)30516-X [pii]
AID - 10.1016/j.eururo.2017.06.021 [doi]
PST - ppublish
SO  - Eur Urol. 2018 Mar;73(3):427-435. doi: 10.1016/j.eururo.2017.06.021. Epub 2017 
      Jul 11.