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dc.contributor.authorJames, NDen_US
dc.contributor.authorPirrie, SJen_US
dc.contributor.authorPope, AMen_US
dc.contributor.authorBarton, Den_US
dc.contributor.authorAndronis, Len_US
dc.contributor.authorGoranitis, Ien_US
dc.contributor.authorCollins, Sen_US
dc.contributor.authorDaunton, Aen_US
dc.contributor.authorMcLaren, Den_US
dc.contributor.authorO'Sullivan, Jen_US
dc.contributor.authorParker, Cen_US
dc.contributor.authorPorfiri, Een_US
dc.contributor.authorStaffurth, Jen_US
dc.contributor.authorStanley, Aen_US
dc.contributor.authorWylie, Jen_US
dc.contributor.authorBeesley, Sen_US
dc.contributor.authorBirtle, Aen_US
dc.contributor.authorBrown, Jen_US
dc.contributor.authorChakraborti, Pen_US
dc.contributor.authorHussain, Sen_US
dc.contributor.authorRussell, Men_US
dc.contributor.authorBillingham, LJen_US
dc.date.accessioned2017-03-01T11:39:59Z
dc.date.issued2016-04en_US
dc.identifier.citationJAMA oncology, 2016, 2 (4), pp. 493 - 499en_US
dc.identifier.issn2374-2437en_US
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/421
dc.identifier.eissn2374-2445en_US
dc.identifier.doi10.1001/jamaoncol.2015.5570en_US
dc.description.abstract<h4>Importance</h4>Bony metastatic castrate-refractory prostate cancer (CRPC) has a poor prognosis and high morbidity. Zoledronic acid (ZA) is commonly combined with docetaxel in practice but lacks evidence that combining is effective, and strontium-89 (Sr89) is generally used palliatively in patients unfit for chemotherapy. Phase 2 analysis of the TRAPEZE trial confirmed combining the agents was safe and feasible, and the objectives of phase 3 include assessment of the treatments on survival.<h4>Objective</h4>To determine clinical effectiveness and cost-effectiveness of combining docetaxel, ZA, and Sr89, all having palliative benefits and used in bony metastatic CRPC to control bone symptoms and, for docetaxel, to prolong survival.<h4>Design, setting, and participants</h4>The TRAPEZE trial is a 2 × 2 factorial trial comparing docetaxel alone or with ZA, Sr89, or both. A cohort of 757 participants were recruited between February 2005 and February 2012 from hospitals in the United Kingdom. Overall, 169 participants (45%) had received palliative radiotherapy, and the median (IQR) prostate-specific antigen level was 146 (51-354). Follow-ups were performed for at least 12 months.<h4>Interventions</h4>Up to 10 cycles of docetaxel alone; docetaxel with ZA; docetaxel with a single Sr89 dose after 6 cycles; or docetaxel with both ZA and Sr89.<h4>Main outcomes and measures</h4>Primary outcomes included clinical progression-free survival (CPFS) (pain progression, skeletal-related events [SREs], or death) and cost-effectiveness. Secondary outcomes included SRE-free interval, pain progression-free interval, total SREs, and overall survival (OS).<h4>Results</h4>Overall, of 757 participants, 349 (46%) completed docetaxel treatment. Median (IQR) age was 68 (63-73) years. Clinical progression-free survival did not reach statistical significance for either Sr89 or ZA. Cox regression analysis adjusted for all stratification variables showed benefit of Sr89 on CPFS (hazard ratio [HR], 0.85; 95% CI, 0.73-0.99; P = .03) and confirmed no effect of ZA (HR, 0.98; 95% CI, 0.85-1.14; P = .81); ZA had a significant effect on SRE-free interval (HR, 0.78; 95% CI, 0.65-0.95; P = .01). For OS, there was no effect of either Sr89 (HR, 0.92; 95% CI, 0.79-1.08; P = 0.34) or ZA (HR, 0.99; 95% CI, 0.84-1.16; P = 0.91).<h4>Conclusions and relevance</h4>Strontium-89 combined with docetaxel improved CPFS but did not improve OS, SRE-free interval, or total SREs; ZA did not improve CPFS or OS but did significantly improve median SRE-free interval and reduced total SREs by around one-third, suggesting a role as postchemotherapy maintenance therapy.<h4>Trial registration</h4>isrctn.com Identifier: ISRCTN12808747.en_US
dc.formatPrinten_US
dc.format.extent493 - 499en_US
dc.languageengen_US
dc.language.isoengen_US
dc.subjectHumansen_US
dc.subjectProstatic Neoplasmsen_US
dc.subjectStrontiumen_US
dc.subjectTaxoidsen_US
dc.subjectDiphosphonatesen_US
dc.subjectImidazolesen_US
dc.subjectAntineoplastic Combined Chemotherapy Protocolsen_US
dc.subjectDisease-Free Survivalen_US
dc.subjectProportional Hazards Modelsen_US
dc.subjectDrug Resistance, Neoplasmen_US
dc.subjectAgeden_US
dc.subjectMiddle Ageden_US
dc.subjectMaleen_US
dc.subjectKaplan-Meier Estimateen_US
dc.subjectDocetaxelen_US
dc.subjectZoledronic Aciden_US
dc.titleClinical Outcomes and Survival Following Treatment of Metastatic Castrate-Refractory Prostate Cancer With Docetaxel Alone or With Strontium-89, Zoledronic Acid, or Both: The TRAPEZE Randomized Clinical Trial.en_US
dc.typeJournal Article
dcterms.dateAccepted2015-11-06en_US
rioxxterms.versionofrecord10.1001/jamaoncol.2015.5570en_US
rioxxterms.licenseref.startdate2016-04en_US
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfJAMA oncologyen_US
pubs.issue4en_US
pubs.notes6 monthsen_US
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Prostate and Bladder Cancer Research
pubs.organisational-group/ICR/Primary Group/Royal Marsden Clinical Units
pubs.publication-statusPublisheden_US
pubs.volume2en_US
pubs.embargo.terms6 monthsen_US
icr.researchteamProstate and Bladder Cancer Researchen_US
dc.contributor.icrauthorParker, Chrisen_US
dc.contributor.icrauthorJames, Nicholasen_US


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