dc.contributor.author | Shimomura, A | |
dc.contributor.author | Yamamoto, N | |
dc.contributor.author | Kondo, S | |
dc.contributor.author | Fujiwara, Y | |
dc.contributor.author | Suzuki, S | |
dc.contributor.author | Yanagitani, N | |
dc.contributor.author | Horiike, A | |
dc.contributor.author | Kitazono, S | |
dc.contributor.author | Ohyanagi, F | |
dc.contributor.author | Doi, T | |
dc.contributor.author | Kuboki, Y | |
dc.contributor.author | Kawazoe, A | |
dc.contributor.author | Shitara, K | |
dc.contributor.author | Ohno, I | |
dc.contributor.author | Banerji, U | |
dc.contributor.author | Sundar, R | |
dc.contributor.author | Ohkubo, S | |
dc.contributor.author | Calleja, EM | |
dc.contributor.author | Nishio, M | |
dc.date.accessioned | 2019-03-15T14:51:59Z | |
dc.date.issued | 2019-03-01 | |
dc.identifier.citation | Molecular cancer therapeutics, 2019, 18 (3), pp. 531 - 540 | |
dc.identifier.issn | 1535-7163 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/3151 | |
dc.identifier.eissn | 1538-8514 | |
dc.identifier.doi | 10.1158/1535-7163.mct-18-0831 | |
dc.description.abstract | HSP90 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. | |
dc.format | Print-Electronic | |
dc.format.extent | 531 - 540 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | AMER ASSOC CANCER RESEARCH | |
dc.rights.uri | https://www.rioxx.net/licenses/under-embargo-all-rights-reserved | |
dc.subject | Cell Line, Tumor | |
dc.subject | Humans | |
dc.subject | Carcinoma, Non-Small-Cell Lung | |
dc.subject | Gastrointestinal Stromal Tumors | |
dc.subject | Benzamides | |
dc.subject | Pyrazoles | |
dc.subject | Protein Kinase Inhibitors | |
dc.subject | Administration, Oral | |
dc.subject | Maximum Tolerated Dose | |
dc.subject | Adult | |
dc.subject | Aged | |
dc.subject | Middle Aged | |
dc.subject | Japan | |
dc.subject | Female | |
dc.subject | Male | |
dc.subject | HSP90 Heat-Shock Proteins | |
dc.subject | United Kingdom | |
dc.title | First-in-Human Phase I Study of an Oral HSP90 Inhibitor, TAS-116, in Patients with Advanced Solid Tumors. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2019-01-11 | |
rioxxterms.versionofrecord | 10.1158/1535-7163.mct-18-0831 | |
rioxxterms.licenseref.uri | https://www.rioxx.net/licenses/under-embargo-all-rights-reserved | |
rioxxterms.licenseref.startdate | 2019-03 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Molecular cancer therapeutics | |
pubs.issue | 3 | |
pubs.notes | Not 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/Cancer Therapeutics | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Medicine Drug Development Unit (de Bono) | |
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.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies/Medicine Drug Development Unit (de Bono) | |
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/Cancer Therapeutics | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Medicine Drug Development Unit (de Bono) | |
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.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies/Medicine Drug Development Unit (de Bono) | |
pubs.publication-status | Published | |
pubs.volume | 18 | |
pubs.embargo.terms | Not known | |
icr.researchteam | Clinical Pharmacology – Adaptive Therapy | |
icr.researchteam | Medicine Drug Development Unit (de Bono) | |
dc.contributor.icrauthor | Banerji, Udai | |