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dc.contributor.authorWilson, RH
dc.contributor.authorEvans, TJ
dc.contributor.authorMiddleton, MR
dc.contributor.authorMolife, LR
dc.contributor.authorSpicer, J
dc.contributor.authorDieras, V
dc.contributor.authorRoxburgh, P
dc.contributor.authorGiordano, H
dc.contributor.authorJaw-Tsai, S
dc.contributor.authorGoble, S
dc.contributor.authorPlummer, R
dc.date.accessioned2018-02-16T10:47:39Z
dc.date.issued2017-03
dc.identifier.citationBritish journal of cancer, 2017, 116 (7), pp. 884 - 892
dc.identifier.issn0007-0920
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/1185
dc.identifier.eissn1532-1827
dc.identifier.doi10.1038/bjc.2017.36
dc.description.abstractBackground This study evaluated safety, pharmacokinetics, and clinical activity of intravenous and oral rucaparib, a poly(ADP-ribose) polymerase inhibitor, combined with chemotherapy in patients with advanced solid tumours.Methods Initially, patients received escalating doses of intravenous rucaparib combined with carboplatin, carboplatin/paclitaxel, cisplatin/pemetrexed, or epirubicin/cyclophosphamide. Subsequently, the study was amended to focus on oral rucaparib (once daily, days 1-14) combined with carboplatin (day 1) in 21-day cycles. Dose-limiting toxicities (DLTs) were assessed in cycle 1 and safety in all cycles.Results Eighty-five patients were enrolled (22 breast, 15 ovarian/peritoneal, and 48 other primary cancers), with a median of three prior therapies (range, 1-7). Neutropenia (27.1%) and thrombocytopenia (18.8%) were the most common grade ⩾3 toxicities across combinations and were DLTs with the oral rucaparib/carboplatin combination. Maximum tolerated dose for the combination was 240 mg per day oral rucaparib and carboplatin area under the curve 5 mg ml -1  min -1 . Oral rucaparib demonstrated dose-proportional kinetics, a long half-life (≈17 h), and good bioavailability (36%). Pharmacokinetics were unchanged by carboplatin coadministration. The rucaparib/carboplatin combination had radiologic antitumour activity, primarily in BRCA1- or BRCA2-mutated breast and ovarian/peritoneal cancers.Conclusions Oral rucaparib can be safely combined with a clinically relevant dose of carboplatin in patients with advanced solid tumours (Trial registration ID: NCT01009190).
dc.formatPrint-Electronic
dc.format.extent884 - 892
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.subjectHumans
dc.subjectNeoplasms
dc.subjectCisplatin
dc.subjectPaclitaxel
dc.subjectCyclophosphamide
dc.subjectCarboplatin
dc.subjectIndoles
dc.subjectEpirubicin
dc.subjectAntineoplastic Combined Chemotherapy Protocols
dc.subjectNeoplasm Staging
dc.subjectPrognosis
dc.subjectAdministration, Oral
dc.subjectSurvival Rate
dc.subjectFollow-Up Studies
dc.subjectTissue Distribution
dc.subjectDose-Response Relationship, Drug
dc.subjectAdult
dc.subjectAged
dc.subjectAged, 80 and over
dc.subjectMiddle Aged
dc.subjectFemale
dc.subjectMale
dc.subjectAdministration, Intravenous
dc.titleA phase I study of intravenous and oral rucaparib in combination with chemotherapy in patients with advanced solid tumours.
dc.typeJournal Article
dcterms.dateAccepted2017-01-20
rioxxterms.versionofrecord10.1038/bjc.2017.36
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2017-03
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfBritish journal of cancer
pubs.issue7
pubs.notesNot known
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.volume116
pubs.embargo.termsNot known
dc.contributor.icrauthorMolife, Rhodaen
dc.contributor.icrauthorMarsden,en


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