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dc.contributor.authorOza, Amit Men
dc.contributor.authorMatulonis, Ursula Aen
dc.contributor.authorAlvarez Secord, Angelesen
dc.contributor.authorNemunaitis, Johnen
dc.contributor.authorRoman, Lynda Den
dc.contributor.authorBlagden, Sarah Pen
dc.contributor.authorBanerjee, Susanaen
dc.contributor.authorMcGuire, William Pen
dc.contributor.authorGhamande, Sharaden
dc.contributor.authorBirrer, Michael Jen
dc.contributor.authorFleming, Gini Fen
dc.contributor.authorMarkham, Merry Jenniferen
dc.contributor.authorHirte, Hal Wen
dc.contributor.authorProvencher, Diane Men
dc.contributor.authorBasu, Bristien
dc.contributor.authorKristeleit, Rebeccaen
dc.contributor.authorArmstrong, Deborah Ken
dc.contributor.authorSchwartz, Benjaminen
dc.contributor.authorBraly, Patriciaen
dc.contributor.authorHall, Geoff Den
dc.contributor.authorNephew, Kenneth Pen
dc.contributor.authorJueliger, Simoneen
dc.contributor.authorOganesian, Aramen
dc.contributor.authorNaim, Sueen
dc.contributor.authorHao, Yongen
dc.contributor.authorKeer, Harolden
dc.contributor.authorAzab, Mohammaden
dc.contributor.authorMatei, Danielaen
dc.date.accessioned2019-12-20T00:31:07Z
dc.date.available2019-12-20T00:31:07Z
dc.date.issued2020-03en
dc.identifier.issn1078-0432
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/300177
dc.description.abstractPURPOSE: Platinum resistance in ovarian cancer (OC) is associated with epigenetic modifications. Hypomethylating agents (HMAs) have been studied as carboplatin re-sensitizing agents in OC. This randomized phase 2 trial compared guadecitabine, a second generation HMA, and carboplatin (G+C) against second-line chemotherapy in women with measurable or detectable platinum-resistant OC. EXPERIMENTAL DESIGN: Patients received either G+C (guadecitabine 30 mg/m2 SC once-daily for 5 days and carboplatin) or treatment of choice (TC; topotecan, pegylated liposomal doxorubicin, paclitaxel, or gemcitabine) in 28-day cycles until progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS); secondary endpoints were RECIST v1.1 and CA-125 response rate, 6-month PFS, and overall survival (OS). RESULTS: Of 100 patients treated, 51 received G+C and 49 received TC, of which 27 crossed over to G+C. The study did not meet its primary endpoint as the median PFS was not statistically different between arms (16.3 weeks vs 9.1 weeks in the G+C and TC groups, respectively; P = 0.07). However, the 6-month PFS rate was significantly higher in the G+C group (37% vs. 11% in TC group; P = 0.003). The incidence of grade 3 or higher toxicity was similar in G+C and TC groups (51% and 49%, respectively), with neutropenia and leukopenia being more frequent in the G+C group. CONCLUSIONS: Although this trial did not show superiority for PFS of G+C versus TC, the 6-month PFS increased in G+C treated patients. Further refinement of this strategy should focus on identification of predictive markers for patient selection.
dc.format.mediumPrint-Electronicen
dc.languageengen
dc.publisherAmerican Association for Cancer Research
dc.rightsAll rights reserved
dc.rights.uri
dc.subjectHumansen
dc.subjectOvarian Neoplasmsen
dc.subjectNeoplasm Recurrence, Localen
dc.subjectPolyethylene Glycolsen
dc.subjectAzacitidineen
dc.subjectPaclitaxelen
dc.subjectCarboplatinen
dc.subjectTopotecanen
dc.subjectDoxorubicinen
dc.subjectDeoxycytidineen
dc.subjectAntineoplastic Combined Chemotherapy Protocolsen
dc.subjectTreatment Outcomeen
dc.subjectSurvival Rateen
dc.subjectEpigenesis, Geneticen
dc.subjectDrug Resistance, Neoplasmen
dc.subjectAdulten
dc.subjectAgeden
dc.subjectAged, 80 and overen
dc.subjectMiddle Ageden
dc.subjectFemaleen
dc.subjectPatient Safetyen
dc.titleA Randomized Phase II Trial of Epigenetic Priming with Guadecitabine and Carboplatin in Platinum-resistant, Recurrent Ovarian Cancer.en
dc.typeArticle
prism.endingPage1016
prism.issueIdentifier5en
prism.publicationDate2020en
prism.publicationNameClinical cancer research : an official journal of the American Association for Cancer Researchen
prism.startingPage1009
prism.volume26en
dc.identifier.doi10.17863/CAM.47248
dcterms.dateAccepted2019-12-05en
rioxxterms.versionofrecord10.1158/1078-0432.ccr-19-1638en
rioxxterms.versionAM
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2020-03en
dc.contributor.orcidOza, Amit M [0000-0002-9510-8641]
dc.contributor.orcidBlagden, Sarah P [0000-0001-8783-3491]
dc.contributor.orcidMarkham, Merry Jennifer [0000-0003-3567-3494]
dc.contributor.orcidHirte, Hal W [0000-0003-2888-4146]
dc.contributor.orcidBasu, Bristi [0000-0002-3562-2868]
dc.contributor.orcidHall, Geoff D [0000-0002-8864-5932]
dc.identifier.eissn1557-3265
rioxxterms.typeJournal Article/Reviewen
cam.orpheus.successThu Jan 30 10:34:49 GMT 2020 - Embargo updated*
rioxxterms.freetoread.startdate2020-12-12


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