First-in-human phase 1 study of novel dUTPase inhibitor TAS-114 in combination with S-1 in Japanese patients with advanced solid tumors.
Adult
Aged
Aged, 80 and over
Antimetabolites, Antineoplastic
/ pharmacokinetics
Drug Combinations
Drug Therapy, Combination
Enzyme Inhibitors
/ pharmacokinetics
Female
Follow-Up Studies
Humans
Male
Maximum Tolerated Dose
Middle Aged
Neoplasms
/ drug therapy
Oxonic Acid
/ pharmacokinetics
Prognosis
Pyrimidines
/ pharmacokinetics
Pyrophosphatases
/ antagonists & inhibitors
Sulfonamides
/ pharmacokinetics
Tegafur
/ pharmacokinetics
Tissue Distribution
Dose-escalation
Phase 1
S-1
Solid tumor
TAS-114
dUTPase
Journal
Investigational new drugs
ISSN: 1573-0646
Titre abrégé: Invest New Drugs
Pays: United States
ID NLM: 8309330
Informations de publication
Date de publication:
06 2019
06 2019
Historique:
received:
27
09
2018
accepted:
12
11
2018
pubmed:
5
12
2018
medline:
23
2
2020
entrez:
5
12
2018
Statut:
ppublish
Résumé
Background This first-in-human phase 1 study assessed the safety of TAS-114, a novel deoxyuridine triphosphatase inhibitor, combined with S-1 to determine its maximum tolerated dose (MTD) and recommended dose (RD). Methods In this dose-escalation study with a 3 + 3 design, TAS-114 and S-1 were concurrently administered orally under fasting conditions at 5-240 mg/m
Identifiants
pubmed: 30511200
doi: 10.1007/s10637-018-0697-3
pii: 10.1007/s10637-018-0697-3
pmc: PMC6538570
doi:
Substances chimiques
Antimetabolites, Antineoplastic
0
Drug Combinations
0
Enzyme Inhibitors
0
Pyrimidines
0
Sulfonamides
0
TAS-114
0
S 1 (combination)
150863-82-4
Tegafur
1548R74NSZ
Oxonic Acid
5VT6420TIG
Pyrophosphatases
EC 3.6.1.-
dUTP pyrophosphatase
EC 3.6.1.23
Banques de données
ClinicalTrials.gov
['NCT01610479']
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
507-518Références
Ann Oncol. 2015 Jul;26(7):1401-8
pubmed: 25908605
Cancer Res. 2000 Jul 1;60(13):3493-503
pubmed: 10910061
Trends Immunol. 2016 Jul;37(7):462-476
pubmed: 27216414
J Clin Oncol. 2008 May 1;26(13):2118-23
pubmed: 18445840
Lancet Oncol. 2016 Jan;17(1):90-8
pubmed: 26617202
Nature. 2004 Nov 18;432(7015):294-7
pubmed: 15549090
Lancet Oncol. 2013 Dec;14(13):1278-86
pubmed: 24225157
Mol Cancer Ther. 2018 Aug;17(8):1683-1693
pubmed: 29748212
Ann Oncol. 2017 Nov 1;28(11):2698-2706
pubmed: 29045553
Mol Pharmacol. 2004 Sep;66(3):620-6
pubmed: 15322254
J Biol Chem. 1996 Mar 29;271(13):7745-51
pubmed: 8631816
Nat Rev Clin Oncol. 2014 May;11(5):282-98
pubmed: 24732946
Cancer Res. 1994 May 1;54(9):2296-8
pubmed: 8162567
Lancet Oncol. 2008 Mar;9(3):215-21
pubmed: 18282805
J Thorac Oncol. 2011 Apr;6(4):790-5
pubmed: 21325974
Mol Cancer Ther. 2008 Sep;7(9):3029-37
pubmed: 18790783
Cancer Sci. 2011 Feb;102(2):478-83
pubmed: 21143703
J Clin Oncol. 1999 Jun;17(6):1760-70
pubmed: 10561213
ChemMedChem. 2016 Mar 4;11(5):450-66
pubmed: 26836578
Jpn J Clin Oncol. 2009 Jan;39(1):2-15
pubmed: 19052037
Lancet Oncol. 2009 Nov;10(11):1063-9
pubmed: 19818685
Nat Rev Cancer. 2003 May;3(5):330-8
pubmed: 12724731
Cancer Chemother Pharmacol. 2014 Mar;73(3):577-83
pubmed: 24452393
J Clin Oncol. 2013 May 1;31(13):1640-8
pubmed: 23547081