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dc.contributor.authorParker, C
dc.contributor.authorFinkelstein, SE
dc.contributor.authorMichalski, JM
dc.contributor.authorO'Sullivan, JM
dc.contributor.authorBruland, Ø
dc.contributor.authorVogelzang, NJ
dc.contributor.authorColeman, RE
dc.contributor.authorNilsson, S
dc.contributor.authorSartor, O
dc.contributor.authorLi, R
dc.contributor.authorSeger, MA
dc.contributor.authorBottomley, D
dc.date.accessioned2016-11-21T13:01:51Z
dc.date.issued2016-11
dc.identifier.citationEuropean urology, 2016, 70 (5), pp. 875 - 883
dc.identifier.issn0302-2838
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/218
dc.identifier.eissn1873-7560
dc.identifier.doi10.1016/j.eururo.2016.06.002
dc.description.abstractBackground The phase 3 ALSYMPCA trial enrolled metastatic castration-resistant prostate cancer patients with or without baseline opioid use.Objective To assess the efficacy and safety of radium-223 dichloride (radium-223) versus placebo in ALSYMPCA patients by baseline opioid use.Design, setting, and participants Nine hundred and twenty one patients enrolled at 136 centers globally.Intervention Radium-223 (50 kBq/kg, intravenous injection) every 4 wk for six cycles or matching placebo, each plus best standard of care.Outcome measurements and statistical analysis Primary endpoint (overall survival [OS]), main secondary efficacy endpoints, and safety were evaluated by baseline opioid use. Additional analyses included time to first opioid use, time to first external beam radiation therapy for bone pain, and safety of concomitant external beam radiation therapy.Results and limitations At baseline, 408 (44%) patients had no pain and no analgesic use or mild pain with nonopioid therapy (World Health Organization ladder pain score 0-1 [nonopioid subgroup]), and 513 (56%) had moderate pain with occasional opioids or severe pain with regular daily opioids (World Health Organization ladder pain score 2-3 [opioid subgroup]). Radium-223 significantly prolonged OS versus placebo in nonopioid (hazard ratio [HR]=0.70; 95% confidence interval [CI]: 0.52-0.93; p=0.013) and opioid (HR=0.68; 95% CI: 0.54-0.86; p=0.001) subgroups, and significantly reduced risk of symptomatic skeletal events versus placebo, regardless of baseline opioid use (nonopioid subgroup: HR=0.56, 95% CI: 0.39-0.82, p=0.002; opioid subgroup: HR=0.72, 95% CI: 0.53-0.98, p=0.038). Time to first opioid use for bone pain was significantly delayed with radium-223 versus placebo (HR=0.62, 95% CI: 0.46-0.85, p=0.002). Adverse event incidences were similar between opioid subgroups.Conclusions Radium-223 versus placebo significantly prolonged OS and reduced symptomatic skeletal event risk with a favorable safety profile in castration-resistant prostate cancer patients with symptomatic bone metastases, regardless of baseline opioid use.Patient summary In this ALSYMPCA opioid subgroup analysis, baseline symptom levels did not appear to impact radium-223 dichloride efficacy or safety.
dc.formatPrint-Electronic
dc.format.extent875 - 883
dc.languageeng
dc.language.isoeng
dc.subjectHumans
dc.subjectBone Neoplasms
dc.subjectRadium
dc.subjectRadioisotopes
dc.subjectAnalgesics, Opioid
dc.subjectAntineoplastic Agents
dc.subjectDrug Monitoring
dc.subjectTreatment Outcome
dc.subjectCombined Modality Therapy
dc.subjectSurvival Analysis
dc.subjectDouble-Blind Method
dc.subjectAged
dc.subjectAged, 80 and over
dc.subjectMiddle Aged
dc.subjectMale
dc.subjectSymptom Assessment
dc.subjectProstatic Neoplasms, Castration-Resistant
dc.titleEfficacy and Safety of Radium-223 Dichloride in Symptomatic Castration-resistant Prostate Cancer Patients With or Without Baseline Opioid Use From the Phase 3 ALSYMPCA Trial.
dc.typeJournal Article
dcterms.dateAccepted2016-06-03
rioxxterms.versionofrecord10.1016/j.eururo.2016.06.002
rioxxterms.licenseref.startdate2016-11
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfEuropean urology
pubs.issue5
pubs.notesNo embargo
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/Royal Marsden Clinical Units
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/Royal Marsden Clinical Units
pubs.publication-statusPublished
pubs.volume70
pubs.embargo.termsNo embargo
dc.contributor.icrauthorParker, Chrisen


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