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dc.contributor.authorTrump, DLen_US
dc.contributor.authorPayne, Hen_US
dc.contributor.authorMiller, Ken_US
dc.contributor.authorde Bono, JSen_US
dc.contributor.authorStephenson, Jen_US
dc.contributor.authorBurris, HAen_US
dc.contributor.authorNathan, Fen_US
dc.contributor.authorTaboada, Men_US
dc.contributor.authorMorris, Ten_US
dc.contributor.authorHubner, Aen_US
dc.date.accessioned2018-06-26T10:41:39Z
dc.date.issued2011-09en_US
dc.identifier.citationThe Prostate, 2011, 71 (12), pp. 1264 - 1275en_US
dc.identifier.issn0270-4137en_US
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/1934
dc.identifier.eissn1097-0045en_US
dc.identifier.doi10.1002/pros.21342en_US
dc.description.abstract<h4>Background</h4>This two-part study assessed the safety and tolerability of combined treatment with zibotentan (ZD4054), a specific endothelin A receptor antagonist, plus docetaxel in patients with metastatic castration-resistant prostate cancer.<h4>Methods</h4>Part A was an open-label, dose-finding phase to determine the safety and toxicity profile of zibotentan in combination with docetaxel. Patients received once-daily oral zibotentan 10 mg (initial cohort) or 15 mg in combination with docetaxel 75 mg/m(2) (administered on day 1 of each 21-day cycle) for up to 10 cycles. Part B was a double-blind phase which evaluated the safety and preliminary activity of zibotentan plus docetaxel. Patients were randomized 2:1 to receive zibotentan (at the highest tolerated dose identified in part A) plus docetaxel or placebo plus docetaxel.<h4>Results</h4>Six patients were enrolled in part A (n  = 3, zibotentan 10 mg; n = 3, zibotentan 15 mg). No dose-limiting toxicity was observed, thus zibotentan 15 mg in combination with docetaxel was evaluated in part B (n = 20, zibotentan plus docetaxel; n = 11, placebo plus docetaxel). CTCAE grade ≥3, most commonly neutropenia or leucopenia, were reported in 10 (50%) and nine (82%) patients in the zibotentan and placebo groups, respectively. One (17%) patient receiving placebo achieved complete response, two (22%) patients receiving zibotentan achieved partial response and stable disease occurred in six (67%) and three (50%) patients receiving zibotentan and placebo, respectively.<h4>Conclusions</h4>The tolerability of zibotentan plus docetaxel was consistent with the known profiles of each drug. Sufficient preliminary activity was seen with this combination to merit continued development.en_US
dc.formatPrint-Electronicen_US
dc.format.extent1264 - 1275en_US
dc.languageengen_US
dc.language.isoengen_US
dc.subjectHumansen_US
dc.subjectAdenocarcinomaen_US
dc.subjectBone Neoplasmsen_US
dc.subjectProstatic Neoplasmsen_US
dc.subjectPainen_US
dc.subjectLeukopeniaen_US
dc.subjectNeutropeniaen_US
dc.subjectTaxoidsen_US
dc.subjectPyrrolidinesen_US
dc.subjectAntineoplastic Agentsen_US
dc.subjectTreatment Outcomeen_US
dc.subjectDrug Therapy, Combinationen_US
dc.subjectOrchiectomyen_US
dc.subjectCohort Studiesen_US
dc.subjectDouble-Blind Methoden_US
dc.subjectDose-Response Relationship, Drugen_US
dc.subjectAgeden_US
dc.subjectAged, 80 and overen_US
dc.subjectMiddle Ageden_US
dc.subjectMaleen_US
dc.subjectEndothelin A Receptor Antagonistsen_US
dc.subjectDocetaxelen_US
dc.titlePreliminary study of the specific endothelin a receptor antagonist zibotentan in combination with docetaxel in patients with metastatic castration-resistant prostate cancer.en_US
dc.typeJournal Article
dcterms.dateAccepted2010-12-20en_US
rioxxterms.versionofrecord10.1002/pros.21342en_US
rioxxterms.licenseref.startdate2011-09en_US
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfThe Prostateen_US
pubs.issue12en_US
pubs.notesNot knownen_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/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Prostate Cancer Targeted Therapy Group
pubs.publication-statusPublisheden_US
pubs.volume71en_US
pubs.embargo.termsNot knownen_US
icr.researchteamProstate Cancer Targeted Therapy Groupen_US
dc.contributor.icrauthorDe Bono, Johannen_US


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