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dc.contributor.authorShimomura, Aen_US
dc.contributor.authorYamamoto, Nen_US
dc.contributor.authorKondo, Sen_US
dc.contributor.authorFujiwara, Yen_US
dc.contributor.authorSuzuki, Sen_US
dc.contributor.authorYanagitani, Nen_US
dc.contributor.authorHoriike, Aen_US
dc.contributor.authorKitazono, Sen_US
dc.contributor.authorOhyanagi, Fen_US
dc.contributor.authorDoi, Ten_US
dc.contributor.authorKuboki, Yen_US
dc.contributor.authorKawazoe, Aen_US
dc.contributor.authorShitara, Ken_US
dc.contributor.authorOhno, Ien_US
dc.contributor.authorBanerji, Uen_US
dc.contributor.authorSundar, Ren_US
dc.contributor.authorOhkubo, Sen_US
dc.contributor.authorCalleja, EMen_US
dc.contributor.authorNishio, Men_US
dc.coverage.spatialUnited Statesen_US
dc.date.accessioned2019-03-15T14:51:59Z
dc.date.issued2019-03en_US
dc.identifierhttps://www.ncbi.nlm.nih.gov/pubmed/30679388en_US
dc.identifier1535-7163.MCT-18-0831en_US
dc.identifier.citationMol Cancer Ther, 2019, 18 (3), pp. 531 - 540en_US
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3151
dc.identifier.eissn1538-8514en_US
dc.identifier.doi10.1158/1535-7163.MCT-18-0831en_US
dc.description.abstractHSP90 is involved in stability and function of cancer-related proteins. This study was conducted to define the MTD, safety, pharmacokinetics, pharmacodynamics, and preliminary antitumor efficacy of TAS-116, a novel class, orally available, highly selective inhibitor of HSP90. Patients with advanced solid tumors received TAS-116 orally once daily (QD, step 1) or every other day (QOD, step 2) in 21-day cycles. Each step comprised a dose escalation phase to determine MTD and an expansion phase at the MTD. In the dose escalation phase, an accelerated dose-titration design and a "3+3" design were used. Sixty-one patients were enrolled in Japan and the United Kingdom. MTD was determined to be 107.5 mg/m2/day for QD, and 210.7 mg/m2/day for QOD. In the expansion phase of step 1, TAS-116 was administered 5 days on/2 days off per week (QD × 5). The most common treatment-related adverse events included gastrointestinal disorders, creatinine increases, AST increases, ALT increases, and eye disorders. Eye disorders have been reported with HSP90 inhibitors; however, those observed with TAS-116 in the expansion phases were limited to grade 1. The systemic exposure of TAS-116 increased dose-proportionally with QD and QOD regimens. Two patients with non-small cell lung cancer and one patient with gastrointestinal stromal tumor (GIST) achieved a confirmed partial response. TAS-116 had an acceptable safety profile with some antitumor activity, supporting further development of this HSP90 inhibitor.This is a result from a first-in-human study, in which the HSP90 inhibitor TAS-116 demonstrated preliminary antitumor efficacy in patients with advanced solid tumors, including those with heavily pretreated GIST.en_US
dc.format.extent531 - 540en_US
dc.languageengen_US
dc.language.isoengen_US
dc.rights.urihttp://www.rioxx.net/licenses/under-embargo-all-rights-reserveden_US
dc.titleFirst-in-Human Phase I Study of an Oral HSP90 Inhibitor, TAS-116, in Patients with Advanced Solid Tumors.en_US
dc.typeJournal Article
dcterms.dateAccepted2019-01-11en_US
rioxxterms.versionofrecord10.1158/1535-7163.MCT-18-0831en_US
rioxxterms.licenseref.startdate2019-03en_US
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfMol Cancer Theren_US
pubs.issue3en_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/Clinical Pharmacology – Adaptive Therapy
pubs.publication-statusPublisheden_US
pubs.volume18en_US
pubs.embargo.termsNot knownen_US
icr.researchteamClinical Pharmacology – Adaptive Therapyen_US
dc.contributor.icrauthorBanerji, Udaien_US


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