First-in-Human Phase I Study of an Oral HSP90 Inhibitor, TAS-116, in Patients with Advanced Solid Tumors.
Administration, Oral
Adult
Aged
Benzamides
/ administration & dosage
Carcinoma, Non-Small-Cell Lung
/ drug therapy
Cell Line, Tumor
Female
Gastrointestinal Stromal Tumors
/ drug therapy
HSP90 Heat-Shock Proteins
/ antagonists & inhibitors
Humans
Japan
Male
Maximum Tolerated Dose
Middle Aged
Protein Kinase Inhibitors
/ administration & dosage
Pyrazoles
/ administration & dosage
United Kingdom
Journal
Molecular cancer therapeutics
ISSN: 1538-8514
Titre abrégé: Mol Cancer Ther
Pays: United States
ID NLM: 101132535
Informations de publication
Date de publication:
03 2019
03 2019
Historique:
received:
25
07
2018
revised:
24
10
2018
accepted:
11
01
2019
pubmed:
27
1
2019
medline:
13
3
2020
entrez:
26
1
2019
Statut:
ppublish
Résumé
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/m
Identifiants
pubmed: 30679388
pii: 1535-7163.MCT-18-0831
doi: 10.1158/1535-7163.MCT-18-0831
doi:
Substances chimiques
Benzamides
0
HSP90 Heat-Shock Proteins
0
Protein Kinase Inhibitors
0
Pyrazoles
0
TAS-116
0
Types de publication
Clinical Trial, Phase I
Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
531-540Subventions
Organisme : Cancer Research UK
ID : 11566
Pays : United Kingdom
Organisme : Department of Health
ID : RP-2016-07-028
Pays : United Kingdom
Informations de copyright
©2019 American Association for Cancer Research.