Effects of Sorafenib on Intra-Tumoral Interstitial Fluid Pressure and Circulating Biomarkers in Patients with Refractory Sarcomas (NCI Protocol 6948).

Raut CP, Boucher Y, Duda DG, Morgan JA, Quek R, Ancukiewicz M, Lahdenranta J, Eder JP, Demetri GD, Jain RK.
Journal   PLoS One.
Species  
Analytes Measured   IL-6 , IL-8 , PlGF , Flt-1 VEGFR1
Matrix Tested   Plasma
Year   2012
Volume   7
Page Numbers   e26331
Application   Cytokines and Chemokines
Abstract
PURPOSE: Sorafenib is a multi-targeted tyrosine kinase inhibitor with therapeutic efficacy in several malignancies. Sorafenib may exert its anti-neoplastic effect in part by altering vascular permeability and reducing intra-tumoral interstitial hypertension. As correlative science with a phase II study in patients with advanced soft-tissue sarcomas (STS), we evaluated the impact of this agent on intra-tumor interstitial fluid pressure (IFP), serum circulating biomarkers, and vascular density.

PATIENTS AND METHODS: Patients with advanced STS with measurable disease and at least one superficial lesion amenable to biopsy received sorafenib 400 mg twice daily. Intratumoral IFP and plasma and circulating cell biomarkers were measured before and after 1-2 months of sorafenib administration. Results were analyzed in the context of the primary clinical endpoint of time-to-progression (TTP).

RESULTS: In 15 patients accrued, the median TTP was 45 days (range 14-228). Intra-tumoral IFP measurements obtained in 6 patients at baseline showed a direct correlation with tumor size. Two patients with stable disease at two months had post-sorafenib IFP evaluations and demonstrated a decline in IFP and vascular density. Sorafenib significantly increased plasma VEGF, PlGF, and SDF1α and decreased sVEGFR-2 levels. Increased plasma SDF1α and decreased sVEGFR-2 levels on day 28 correlated with disease progression.

CONCLUSIONS: Pretreatment intra-tumoral IFP correlated with tumor size and decreased in two evaluable patients with SD on sorafenib. Sorafenib also induced changes in circulating biomarkers consistent with expected VEGF pathway blockade, despite the lack of more striking clinical activity in this small series.

View Publications

Related Products

U-PLEX Angiogenesis Combo 1 (human)
FGF (basic), PlGF, Tie-2, VEGF-A, VEGF-D | Human
Multiplex
NEW
U-PLEX Adipokine Combo 1 (mouse)
BDNF, IL-1β, IL-6, IL-10, Insulin, Leptin, MCP-1, TNF-α | Mouse
Multiplex
NEW
U-PLEX CAR-T Cell Safety Combo 1 (human)
GM-CSF, IFN-γ, IL-1β, IL-6, IL-10, MCP-1, TNF-α | Human
Multiplex
NEW
U-PLEX CAR-T Cell Efficacy Combo 1 (human)
Granzyme B, IFN-γ, IL-2, IL-6, IL-12p70, IP-10, Perforin, TNF-α | Human
Multiplex
NEW
U-PLEX Macrophage M1 Combo 1 (mouse)
IL-1β, IL-6, IL-12p70, IL-15, IL-23, IP-10, MCP-1, MIP-1α, TNF-α | Mouse
Multiplex
NEW
U-PLEX Metabolic Hormone Combo 1 (mouse)
C-Peptide, Ghrelin (active), GLP-1 (active), Glucagon, IL-6, Insulin, Leptin, MCP-1, PYY (total), TNF-α | Mouse
Multiplex
NEW
U-PLEX TBI Combo 1 (human)
CD40L (soluble), Fractalkine, IFN-γ, IL-1β, IL-6, IL-18, MCP-1, RANKL/TNFSF11, TNF-α, VEGF-D | Human
Multiplex
NEW
U-PLEX Proinflam Combo 1 (mouse)
IFN-γ, IL-1β, IL-2, IL-6, IL-10, IL-12p70, IL-17A, IP-10, MCP-1, TNF-α | Mouse
Multiplex
NEW
U-PLEX Viral Combo 1 (NHP)
G-CSF, GM-CSF, IFN-α2a, IFN-γ, IL-1β, IL-1RA, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12p70, IP-10, MCP-1, MIP-1α, TNF-α, VEGF-A | Non-human primate
Multiplex
NEW
U-PLEX Viral Combo 1 (human)
G-CSF, GM-CSF, IFN-α2a, IFN-β, IFN-γ, IL-1β, IL-1RA, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12p70, IP-10, MCP-1, MIP-1α, TNF-α, VEGF-A | Human
Multiplex
NEW
U-PLEX Oncolysis Combo 1 (human)
CTLA-4, IFN-α2a, IFN-β, IL-1β, IL-2Rα, IL-6, IL-8, IP-10, LAG3, MIP-1α, PD1 (epitope 1), TIGIT | Human
Multiplex
NEW
U-PLEX Metastasis Combo 1 (human)
E-Selectin, MMP-1, MMP-2, MMP-7, MMP-9 (total), P-Selectin, VEGFR-1/Flt-1 | Human
Multiplex
NEW
U-PLEX Macrophage M1 Combo 1 (human)
IL-1β, IL-6, IL-12p70, IL-18, IL-23, IP-10, MCP-1, MIP-1α, TNF-α | Human
Multiplex
NEW
S-PLEX Proinflammatory Panel 1 (human) Kit
IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-10, IL-12p70, IL-17A, TNF-α | Human
Multiplex
NEW
R-PLEX Mouse PlGF Antibody Set
PlGF | Mouse
R-PLEX Mouse PlGF Assay
PlGF | Mouse
Singleplex
U-PLEX Human VEGFR-1/Flt-1 Antibody Set
VEGFR-1/Flt-1 | Human
U-PLEX Human VEGFR-1/Flt-1 Assay
VEGFR-1/Flt-1 | Human
Singleplex
U-PLEX Human VEGFR-1/Flt-1 384-well Assay
VEGFR-1/Flt-1 | Human
Singleplex
U-PLEX Mouse IL-6 384-Well Assay
IL-6 | Mouse
Singleplex
U-PLEX NHP IL-8 384-Well Assay
IL-8 | Non-human primate
Singleplex
U-PLEX NHP IL-6 384-Well Assay
IL-6 | Non-human primate
Singleplex
R-PLEX Mouse VEGFR-1/Flt-1 Antibody Set
VEGFR-1/Flt-1 | Mouse
R-PLEX Mouse VEGFR-1/Flt-1 Assay
VEGFR-1/Flt-1 | Mouse
Singleplex
U-PLEX Human PlGF 384-Well Assay
PlGF | Human
Singleplex
U-PLEX Human IL-8 384-Well Assay
IL-8 | Human
Singleplex
U-PLEX Human IL-6 384-Well Assay
IL-6 | Human
Singleplex
S-PLEX NHP IL-6 Kit
IL-6 | Non-human primate
Singleplex
S-PLEX Human IL-6 Kit
IL-6 | Human
Singleplex
U-PLEX Human PlGF Antibody Set
PlGF | Human
U-PLEX Human PlGF Assay
PlGF | Human
Singleplex
V-PLEX Plus Viral Panel 3 Human Kit
IFN-γ, IL-1β, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, TNF-α | Human
Multiplex
V-PLEX Plus Viral Panel 3 NHP Kit
IFN-γ, IL-1β, IL-5, IL-6, IL-8, IL-10 | Non-human primate
Multiplex
V-PLEX Viral Panel 3 NHP Kit
IFN-γ, IL-1β, IL-5, IL-6, IL-8, IL-10 | Non-human primate
Multiplex
V-PLEX Viral Panel 3 Human Kit
IFN-γ, IL-1β, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, TNF-α | Human
Multiplex
V-PLEX Viral Panel 2 NHP Kit
IFN-γ, IL-1β, IL-6, IL-8, IL-10 | Non-human primate
Multiplex
V-PLEX Viral Panel 2 Human Kit
IFN-γ, IL-1β, IL-4, IL-6, IL-8, IL-10, TNF-α | Human
Multiplex
V-PLEX Viral Panel 1 NHP Kit
IL-1β, IL-6, IL-8 | Non-human primate
Multiplex
V-PLEX Viral Panel 1 Human Kit
IL-1β, IL-6, IL-8, TNF-α | Human
Multiplex
V-PLEX Plus Viral Panel 2 NHP Kit
IFN-γ, IL-1β, IL-6, IL-8, IL-10 | Non-human primate
Multiplex
V-PLEX Plus Viral Panel 2 Human Kit
IFN-γ, IL-1β, IL-4, IL-6, IL-8, IL-10, TNF-α | Human
Multiplex
V-PLEX Plus Viral Panel 1 NHP Kit
IL-1β, IL-6, IL-8 | Non-human primate
Multiplex
V-PLEX Plus Viral Panel 1 Human Kit
IL-1β, IL-6, IL-8, TNF-α | Human
Multiplex
R-PLEX Rat IL-6 Assay
IL-6 | Rat
Singleplex
R-PLEX Rat IL-6 Antibody Set
IL-6 | Rat
U-PLEX Human IL-8 Antibody Set
IL-8 | Human
U-PLEX Human IL-6 Antibody Set
IL-6 | Human
Human PlGF Antibody
PlGF
Human Flt-1 Antibody
VEGFR-1/Flt-1
Rat IL-6 Antibody
IL-6
Proinflammatory Panel 1 Rat Control Pack
IFN-γ, IL-1β, IL-4, IL-5, IL-6, IL-10, IL-13, KC/GRO, TNF-α | Rat
Proinflammatory Panel 1 Mouse Control Pack
IFN-γ, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12p70, KC/GRO, TNF-α | Mouse
Chemokine Panel 1 Human Control Pack
Eotaxin, Eotaxin-3, IL-8, IP-10, MCP-1, MCP-4, MDC, MIP-1α, MIP-1β, TARC | Human
Human IL-8 Antibody Bulk Product
IL-8
Human IL-6 Antibody Bulk Product
IL-6
Proinflammatory Panel 1 Human Control Pack
IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, TNF-α | Human
Mouse IL-6 Antibody
IL-6
V-PLEX Human PlGF Kit
PlGF | Human
Singleplex
Angiogenesis Control Pack 1
FGF (basic), PlGF, Tie-2, VEGF-A, VEGF-C, VEGF-D, VEGFR-1/Flt-1 | Human
Browse Our Products

By Analytes
By Applications
Search
Meso Scale Japan 株式会社