A Phase II and Biomarker Study of Sorafenib Combined with Modified FOLFOX in Patients with Advanced Hepatocellular Carcinoma.
Adult
Aged
Antineoplastic Combined Chemotherapy Protocols
/ administration & dosage
Biomarkers, Tumor
/ blood
CD56 Antigen
Carcinoma, Hepatocellular
/ blood
Cell Proliferation
/ drug effects
Drug-Related Side Effects and Adverse Reactions
/ classification
Female
Fluorouracil
/ administration & dosage
Humans
Killer Cells, Natural
/ drug effects
Leucovorin
/ administration & dosage
Liver Neoplasms
/ blood
Male
Middle Aged
Organoplatinum Compounds
/ administration & dosage
Placenta Growth Factor
/ blood
Sorafenib
/ administration & dosage
T-Lymphocytes, Regulatory
/ drug effects
Vascular Endothelial Growth Factor Receptor-1
/ blood
Vascular Endothelial Growth Factor Receptor-2
/ blood
Journal
Clinical cancer research : an official journal of the American Association for Cancer Research
ISSN: 1557-3265
Titre abrégé: Clin Cancer Res
Pays: United States
ID NLM: 9502500
Informations de publication
Date de publication:
01 01 2019
01 01 2019
Historique:
received:
19
03
2018
revised:
14
06
2018
accepted:
31
08
2018
pubmed:
8
9
2018
medline:
27
2
2020
entrez:
8
9
2018
Statut:
ppublish
Résumé
Sorafenib is a standard first-line treatment for advanced hepatocellular carcinoma (HCC). The phase III SHARP trial showed a median time-to-progression (mTTP) of 5.5 months, overall response rate (ORR) of 2%, and median overall survival (mOS) of 10.7 months with sorafenib. FOLFOX4 has shown modest activity in advanced HCC. We evaluated the combination of sorafenib and modified (m)FOLFOX in a single-arm, multicenter phase II study. The study included Child-Pugh A patients with advanced HCC and no prior systemic therapies. Patients received sorafenib 400 mg twice a day for 2 weeks, followed by concurrent mFOLFOX [5-fluorouracil (5-FU) 1,200 mg/m The study enrolled 40 patients: HCV/EtOH/HBV, 43%/28%/13%; Child-Pugh A5, 70%. Notable grade 3/4 adverse events (AE) included AST/ALT elevation (28%/15%), diarrhea (13%), hyperbilirubinemia (10%), hand-foot syndrome (8%), and bleeding (8%). mTTP was 7.7 months [95% confidence interval (CI): 4.4-8.9], ORR 18%, and mOS 15.1 months (7.9-16.9). Sorafenib + mFOLFOX increased plasma PlGF, VEGF-D, sVEGFR1, IL12p70, and CAIX and CD4 Sorafenib + mFOLFOX met the prespecified endpoint with encouraging efficacy but moderate hepatotoxicity. Thus, this regimen may be effective in select patients with adequate liver reserve. Biomarker evaluations suggested a correlation between time-to-progression (TTP) and angiogenic biomarkers and circulating Tregs.
Identifiants
pubmed: 30190369
pii: 1078-0432.CCR-18-0847
doi: 10.1158/1078-0432.CCR-18-0847
pmc: PMC6320284
mid: NIHMS1506046
doi:
Substances chimiques
Biomarkers, Tumor
0
CD56 Antigen
0
NCAM1 protein, human
0
Organoplatinum Compounds
0
PGF protein, human
0
Placenta Growth Factor
144589-93-5
Sorafenib
9ZOQ3TZI87
KDR protein, human
EC 2.7.10.1
Vascular Endothelial Growth Factor Receptor-1
EC 2.7.10.1
Vascular Endothelial Growth Factor Receptor-2
EC 2.7.10.1
Leucovorin
Q573I9DVLP
Fluorouracil
U3P01618RT
Types de publication
Clinical Trial, Phase II
Journal Article
Randomized Controlled Trial
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
80-89Subventions
Organisme : NCI NIH HHS
ID : P01 CA080124
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA208205
Pays : United States
Organisme : NCI NIH HHS
ID : R35 CA197743
Pays : United States
Informations de copyright
©2018 American Association for Cancer Research.
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