Integrating cytokines and angiogenic factors and tumour bulk with selected clinical criteria improves determination of prognosis in advanced renal cell carcinoma

In two clinical trials of the vascular endothelial growth factor (VEGF) receptor inhibitor pazopanib in advanced renal cell carcinoma (mRCC), we found interleukin-6 as predictive of pazopanib benefit. We evaluated the prognostic significance of candidate cytokines and angiogenic factors (CAFs) ident...

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Bibliographic Details
Published in:British journal of cancer 2017-08, Vol.117 (4), p.478-484
Main Authors: Zurita, A J, Gagnon, R C, Liu, Y, Tran, H T, Figlin, R A, Hutson, T E, D'Amelio, Jr, A M, Sternberg, C N, Pandite, L N, Heymach, J V
Format: Article
Language:English
Subjects:
Adult
Aged
Aged, 80 and over
Angiogenesis
Antineoplastic Agents - therapeutic use
Carcinoma, Renal Cell - blood
Carcinoma, Renal Cell - drug therapy
Carcinoma, Renal Cell - mortality
Carcinoma, Renal Cell - pathology
Clinical Study
Clinical trials
Criteria
Cytokines
Cytokines - blood
E-selectin
E-Selectin - blood
Enzyme-linked immunosorbent assay
Female
Hemoglobins - metabolism
Hepatocyte growth factor
Hepatocyte Growth Factor - blood
Humans
Interleukin 6
Interleukin 8
Interleukin-6 - blood
Interleukin-8 - blood
Kidney cancer
Kidney Neoplasms - blood
Kidney Neoplasms - drug therapy
Kidney Neoplasms - mortality
Kidney Neoplasms - pathology
L-Lactate Dehydrogenase - blood
Leukocyte Count
Male
Medical prognosis
Metastases
Middle Aged
Neutrophils
Osteopontin
Osteopontin - blood
Prognosis
Pyrimidines - therapeutic use
Renal cell carcinoma
Sulfonamides - therapeutic use
Survival Rate
Time-to-Treatment
Tissue inhibitor of metalloproteinase 1
Tissue Inhibitor of Metalloproteinase-1 - blood
Tumor Burden
Tumors
Vascular endothelial growth factor
Vascular Endothelial Growth Factor A - blood
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Summary:In two clinical trials of the vascular endothelial growth factor (VEGF) receptor inhibitor pazopanib in advanced renal cell carcinoma (mRCC), we found interleukin-6 as predictive of pazopanib benefit. We evaluated the prognostic significance of candidate cytokines and angiogenic factors (CAFs) identified in that work relative to accepted clinical parameters. Seven preselected plasma CAFs (interleukin-6, interleukin-8, osteopontin, VEGF, hepatocyte growth factor, tissue inhibitor of metalloproteinases (TIMP-1), and E-selectin) were measured using multiplex ELISA in plasma collected pretreatment from 343 mRCC patients participating in the phase 3 registration trial of pazopanib vs placebo (NCT00334282). Tumour burden (per sum of longest diameters (SLD)) and 10 other clinical factors were also analysed for association with overall survival (OS; based on initial treatment assignment). Osteopontin, interleukin-6, and TIMP-1 were independently associated with OS in multivariable analysis. A model combining the three CAFs and five clinical variables (including SLD) had higher prognostic accuracy than the International Metastatic Renal Cell Carcinoma Database Consortium criteria (concordance-index 0.75 vs 0.67, respectively), and distinguished two groups of patients within the original intermediate risk category. A prognostic model incorporating osteopontin, interleukin-6, TIMP-1, tumour burden, and selected clinical criteria increased prognostic accuracy for OS determination in mRCC patients.
ISSN:0007-0920
1532-1827
DOI:10.1038/bjc.2017.206