Luminespib plus pemetrexed in patients with non-squamous non-small cell lung cancer.
Aged
Aged, 80 and over
Antineoplastic Combined Chemotherapy Protocols
/ adverse effects
Biomarkers, Tumor
Carcinoma, Non-Small-Cell Lung
/ drug therapy
Female
Humans
Isoxazoles
/ administration & dosage
Lung Neoplasms
/ drug therapy
Male
Middle Aged
Molecular Targeted Therapy
Neoplasm Staging
Pemetrexed
/ administration & dosage
Resorcinols
/ administration & dosage
Treatment Outcome
Dihydrofolate Reductase (DHFR)
Heat Shock Protein 90 (HSP90) Inhibitor
Luminespib (AUY922)
Non-small cell lung cancer (NSCLC)
Pemetrexed
Targeted therapy
Journal
Lung cancer (Amsterdam, Netherlands)
ISSN: 1872-8332
Titre abrégé: Lung Cancer
Pays: Ireland
ID NLM: 8800805
Informations de publication
Date de publication:
09 2019
09 2019
Historique:
received:
13
12
2018
revised:
21
03
2019
accepted:
13
05
2019
entrez:
27
8
2019
pubmed:
27
8
2019
medline:
14
7
2020
Statut:
ppublish
Résumé
Luminespib (AUY922) is a second-generation heat shock protein 90 (HSP90) inhibitor with demonstrated activity in non-small cell lung cancer (NSCLC). Since luminespib reduces levels of dihydrofolate reductase (DHFR), a key enzymatic target of pemetrexed, we assessed the safety and tolerability of luminespib in combination with pemetrexed in patients with previously treated metastatic non-squamous non-small cell lung cancer (NSCLC). We also sought to study the pharmacokinetics and correlate tumor dihydrofolate reductase (DHFR) expression with clinical response. Patients received weekly luminespib at either 40 mg/m Two-dose limiting toxicities (DLTs) were experienced in the 70 mg/m2 cohort, therefore the MTD was determined to be 55 mg/m In patients with previously treated metastatic NSCLC, the MTD of luminespib in combination with pemetrexed was 55 mg/m
Sections du résumé
BACKGROUND
Luminespib (AUY922) is a second-generation heat shock protein 90 (HSP90) inhibitor with demonstrated activity in non-small cell lung cancer (NSCLC). Since luminespib reduces levels of dihydrofolate reductase (DHFR), a key enzymatic target of pemetrexed, we assessed the safety and tolerability of luminespib in combination with pemetrexed in patients with previously treated metastatic non-squamous non-small cell lung cancer (NSCLC). We also sought to study the pharmacokinetics and correlate tumor dihydrofolate reductase (DHFR) expression with clinical response.
METHODS
Patients received weekly luminespib at either 40 mg/m
RESULTS
Two-dose limiting toxicities (DLTs) were experienced in the 70 mg/m2 cohort, therefore the MTD was determined to be 55 mg/m
CONCLUSION
In patients with previously treated metastatic NSCLC, the MTD of luminespib in combination with pemetrexed was 55 mg/m
Identifiants
pubmed: 31446981
pii: S0169-5002(19)30458-1
doi: 10.1016/j.lungcan.2019.05.022
pii:
doi:
Substances chimiques
5-(2,4-dihydroxy-5-isopropylphenyl)-4-(4-morpholin-4-ylmethylphenyl)isoxazole-3-carboxylic acid ethylamide
0
Biomarkers, Tumor
0
Isoxazoles
0
Resorcinols
0
Pemetrexed
04Q9AIZ7NO
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
104-109Informations de copyright
Copyright © 2019 Elsevier B.V. All rights reserved.