Phase II study of cediranib, an oral pan-vascular endothelial growth factor receptor tyrosine kinase inhibitor, in patients with recurrent glioblastoma.

Batchelor, T.T., Duda, D.G., di Tomaso, E., Ancukiewicz, M., Plotkin, S.R., Gerstner, E., Eichler, A.F., Drappatz, J., Hochberg, F.H., Benner, T., Louis, D.N., Cohen, K.S., Chea, H., Exarhopoulos, A., Loeffler, J.S., Moses, M.A., Ivy, P., Sorensen, A.G., Wen, P.Y., Jain, R.K.
Journal   J Clin Oncol.
Species  
Analytes Measured   IL-6 , IL-8 , , MMP-2 , PlGF , Flt-1 VEGFR1
Matrix Tested   Plasma
Year   2010
Volume   28
Page Numbers   2817-2823
Application   Cytokines and Chemokines
Abstract
PURPOSE: Glioblastoma is an incurable solid tumor characterized by increased expression of vascular endothelial growth factor (VEGF). We performed a phase II study of cediranib in patients with recurrent glioblastoma.

METHODS: Cediranib, an oral pan-VEGF receptor tyrosine kinase inhibitor, was administered (45 mg/d) until progression or unacceptable toxicity to patients with recurrent glioblastoma. The primary end point was the proportion of patients alive and progression free at 6 months (APF6). We performed magnetic resonance imaging (MRI) and plasma and urinary biomarker evaluations at multiple time points.

RESULTS: Thirty-one patients with recurrent glioblastoma were accrued. APF6 after cediranib was 25.8%. Radiographic partial responses were observed by MRI in 17 (56.7%) of 30 evaluable patients using three-dimensional measurements and in eight (27%) of 30 evaluable patients using two-dimensional measurements. For the 15 patients who entered the study taking corticosteroids, the dose was reduced (n = 10) or discontinued (n = 5). Toxicities were manageable. Grade 3/4 toxicities included hypertension (four of 31; 12.9%); diarrhea (two of 31; 6.4%); and fatigue (six of 31; 19.4%). Fifteen (48.4%) of 31 patients required at least one dose reduction and 15 patients required temporary drug interruptions due to toxicity. Drug interruptions were not associated with outcome. Changes in plasma placental growth factor, basic fibroblast growth factor, matrix metalloproteinase (MMP) -2, soluble VEGF receptor 1, stromal cell-derived factor-1alpha, and soluble Tek/Tie2 receptor and in urinary MMP-9/neutrophil gelatinase-associated lipocalin activity after cediranib were associated with radiographic response or survival.

CONCLUSION: Cediranib monotherapy for recurrent glioblastoma is associated with encouraging proportions of radiographic response, 6-month progression-free survival, and a steroid-sparing effect with manageable toxicity. We identified early changes in circulating molecules as potential biomarkers of response to cediranib. The efficacy of cediranib and the predictive value of these candidate biomarkers will be explored in prospective trials.

View Publications

Related Products

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 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 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 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 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 (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 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 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 MMP-2 Antibody Set
MMP-2 | Human
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 Human MMP-2 Assay
MMP-2 | Human
Singleplex
U-PLEX Human MMP-2 384-well Assay
MMP-2 | 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 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
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
R-PLEX Rat IL-6 Assay
IL-6 | Rat
Singleplex
R-PLEX Rat IL-6 Antibody Set
IL-6 | Rat
U-PLEX Mouse IL-6 Antibody Set
IL-6 | Mouse
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
Customer Service/Orders


Scientific/Technical Support


Instrument Support


Company Headquarters