Show simple item record

dc.contributor.authorChi, KN
dc.contributor.authorHigano, CS
dc.contributor.authorBlumenstein, B
dc.contributor.authorFerrero, J-M
dc.contributor.authorReeves, J
dc.contributor.authorFeyerabend, S
dc.contributor.authorGravis, G
dc.contributor.authorMerseburger, AS
dc.contributor.authorStenzl, A
dc.contributor.authorBergman, AM
dc.contributor.authorMukherjee, SD
dc.contributor.authorZalewski, P
dc.contributor.authorSaad, F
dc.contributor.authorJacobs, C
dc.contributor.authorGleave, M
dc.contributor.authorde Bono, JS
dc.date.accessioned2018-02-16T10:14:11Z
dc.date.issued2017-04
dc.identifier.citationThe Lancet. Oncology, 2017, 18 (4), pp. 473 - 485
dc.identifier.issn1470-2045
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/1164
dc.identifier.eissn1474-5488
dc.identifier.doi10.1016/s1470-2045(17)30168-7
dc.description.abstractBackground Clusterin is a chaperone protein associated with treatment resistance and upregulated by apoptotic stressors such as chemotherapy. Custirsen is a second-generation antisense oligonucleotide that inhibits clusterin production. The aim of the SYNERGY trial was to investigate the effect of custirsen in combination with docetaxel and prednisone on overall survival in patients with metastatic castration-resistant prostate cancer.Methods SYNERGY was a phase 3, multicentre, open-label, randomised trial set at 134 study centres in 12 countries. Patients were eligible for participation if they had: metastatic castration-resistant prostate cancer and had received no previous chemotherapy; prostate-specific antigen greater than 5 ng/mL; and a Karnofsky performance score of 70% or higher. Patients were randomly assigned 1:1 centrally to either the docetaxel, prednisone, and custirsen combination or docetaxel and prednisone alone. Patients were not masked to treatment allocation. Randomisation was stratified by opioid use for cancer-related pain and radiographic evidence of progression. All patients received docetaxel 75 mg/m<sup>2</sup> intravenously with 5 mg of prednisone orally twice daily. Patients assigned docetaxel, prednisone, and custirsen received weekly doses of custirsen 640 mg intravenously after three loading doses of 640 mg. The primary endpoint was overall survival analysed in the intention-to-treat population. Patients who received at least one study dose were included in the safety analysis set. This trial is registered with ClinicalTrials.gov, number NCT01188187. The trial is completed and final analyses are reported here.Findings Between Dec 10, 2010, and Nov 7, 2012, 1022 patients were enrolled to the trial, of whom 510 were assigned docetaxel, prednisone, and custirsen and 512 were allocated docetaxel and prednisone. No difference in overall survival was recorded between the two groups (median survival 23·4 months [95% CI 20·9-24·8] with docetaxel, prednisone, and custirsen vs 22·0 months [19·5-24·0] with docetaxel and prednisone; hazard ratio [HR] 0·93, 95% CI 0·79-1·10; p=0·415). The most common adverse events of grade 3 or worse in the docetaxel, prednisone and custirsen group (n=501) compared with the docetaxel and prednisone alone group (n=499) were neutropenia (grade 3, 63 [13%] vs 28 [6%]; grade 4, 98 [20%] vs 77 [15%]), febrile neutropenia (grade 3, 52 [10%] vs 31 [6%]; grade 4, four [1%] vs two [<1%]), and fatigue (grade 3, 53 [11%] vs 41 [8%]; grade 4, three [1%] vs one [<1%]). One or more serious adverse events were reported for 214 (43%) of 501 patients treated with docetaxel, prednisone, and custirsen and 181 (36%) of 499 receiving docetaxel and prednisone alone. Adverse events were attributable to 23 (5%) deaths in the docetaxel, prednisone, and custirsen group and 24 (5%) deaths in the docetaxel and prednisone alone group.Interpretation Addition of custirsen to first-line docetaxel and prednisone was reasonably well tolerated, but overall survival was not significantly longer for patients with metastatic castration-resistant prostate cancer treated with this combination, compared with patients treated with docetaxel and prednisone alone.Funding OncoGenex Technologies.
dc.formatPrint-Electronic
dc.format.extent473 - 485
dc.languageeng
dc.language.isoeng
dc.subjectHumans
dc.subjectBone Neoplasms
dc.subjectLymphatic Metastasis
dc.subjectDisease Progression
dc.subjectTaxoids
dc.subjectPrednisone
dc.subjectThionucleotides
dc.subjectAntineoplastic Combined Chemotherapy Protocols
dc.subjectPrognosis
dc.subjectSurvival Rate
dc.subjectFollow-Up Studies
dc.subjectAdult
dc.subjectAged
dc.subjectAged, 80 and over
dc.subjectMiddle Aged
dc.subjectMale
dc.subjectNeoplasm Grading
dc.subjectProstatic Neoplasms, Castration-Resistant
dc.subjectDocetaxel
dc.titleCustirsen in combination with docetaxel and prednisone for patients with metastatic castration-resistant prostate cancer (SYNERGY trial): a phase 3, multicentre, open-label, randomised trial.
dc.typeJournal Article
dcterms.dateAccepted2017-01-20
rioxxterms.versionofrecord10.1016/s1470-2045(17)30168-7
rioxxterms.licenseref.startdate2017-04
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfThe Lancet. Oncology
pubs.issue4
pubs.notesNot known
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/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Prostate Cancer Targeted Therapy 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/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Prostate Cancer Targeted Therapy Group
pubs.organisational-group/ICR/Primary Group/Royal Marsden Clinical Units
pubs.publication-statusPublished
pubs.volume18en_US
pubs.embargo.termsNot known
icr.researchteamProstate Cancer Targeted Therapy Groupen_US
dc.contributor.icrauthorDe Bono, Johannen
dc.contributor.icrauthorMarsden,en


Files in this item

Thumbnail

This item appears in the following collection(s)

Show simple item record