Optimizing the Therapeutic Window of Targeted Drugs in Oncology: Potency-Guided First-in-Human Studies.
Antineoplastic Agents
/ administration & dosage
Area Under Curve
Cell Line, Tumor
Clinical Trials, Phase I as Topic
/ methods
Dose-Response Relationship, Drug
Humans
Inhibitory Concentration 50
Maximum Tolerated Dose
Neoplasms
/ drug therapy
Poly(ADP-ribose) Polymerase Inhibitors
/ administration & dosage
Protein Kinase Inhibitors
/ administration & dosage
Research Design
Journal
Clinical and translational science
ISSN: 1752-8062
Titre abrégé: Clin Transl Sci
Pays: United States
ID NLM: 101474067
Informations de publication
Date de publication:
03 2021
03 2021
Historique:
received:
21
05
2020
accepted:
07
09
2020
pubmed:
14
10
2020
medline:
15
12
2021
entrez:
13
10
2020
Statut:
ppublish
Résumé
Many targeted therapies are administered at or near the maximum tolerated dose (MTD). With the advent of precision medicine, a larger therapeutic window is expected. Therefore, dose optimization will require a new approach to early clinical trial design. We analyzed publicly available data for 21 therapies targeting six kinases, and four poly (ADP-ribose) polymerase inhibitors, focusing on potency and exposure to gain insight into dose selection. The free average steady-state concentration (C
Identifiants
pubmed: 33048459
doi: 10.1111/cts.12902
pmc: PMC7993318
doi:
Substances chimiques
Antineoplastic Agents
0
Poly(ADP-ribose) Polymerase Inhibitors
0
Protein Kinase Inhibitors
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
536-543Informations de copyright
© 2020 Tango Therapeutics. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of the American Society for Clinical Pharmacology and Therapeutics.
Références
Int J Cell Biol. 2015;2015:798936
pubmed: 26689952
Oncotarget. 2018 Oct 16;9(81):35226-35240
pubmed: 30443290
Cancer Treat Rev. 2011 Jun;37(4):291-9
pubmed: 21078547
PLoS One. 2015 Oct 27;10(10):e0140988
pubmed: 26505995
J Glob Oncol. 2019 Jul;5:1-5
pubmed: 31348737
J Med Chem. 2016 Mar 10;59(5):1984-2004
pubmed: 26789553
Br J Clin Pharmacol. 2014 Sep;78(3):543-55
pubmed: 24617631
Mol Cancer Ther. 2014 May;13(5):1117-29
pubmed: 24608574
Int J Oncol. 2011 Jul;39(1):23-31
pubmed: 21523318
Clin Transl Sci. 2018 Jul;11(4):345-351
pubmed: 29392871
Oncotarget. 2017 May 10;8(41):69493-69507
pubmed: 29050219
J Med Chem. 2014 Oct 23;57(20):8249-67
pubmed: 25271963
Cancer Sci. 2016 Jan;107(1):45-52
pubmed: 26545934
Cancer Discov. 2014 Sep;4(9):1046-61
pubmed: 24893891
J Med Chem. 2009 Nov 26;52(22):7170-85
pubmed: 19873981
Stat Biopharm Res. 2016;8(2):161-170
pubmed: 27516848
Clin Cancer Res. 2012 Jun 1;18(11):3090-9
pubmed: 22496205
Oncotarget. 2015 Nov 17;6(36):38789-803
pubmed: 26515464
Clin Cancer Res. 2018 Sep 15;24(18):4357-4364
pubmed: 29661774
Breast Cancer Res. 2009;11(5):R77
pubmed: 19874578
Drug Metab Dispos. 2015 Jan;43(1):54-62
pubmed: 25349124
Cancer Res. 2003 Jan 15;63(2):375-81
pubmed: 12543790
ACS Med Chem Lett. 2015 Mar 18;6(5):543-7
pubmed: 26005530
Clin Cancer Res. 2016 Jun 1;22(11):2630-8
pubmed: 27250934
Clin Cancer Res. 2016 Jun 1;22(11):2613-7
pubmed: 27250931
J Thorac Oncol. 2010 Jul;5(7):1048-53
pubmed: 20512075
Clin Cancer Res. 2017 Sep 15;23(18):5339-5348
pubmed: 28611198
Drug Metab Dispos. 2012 May;40(5):919-27
pubmed: 22315332