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Br J Cancer. 2017 Aug 8;117(4):478-484. doi: 10.1038/bjc.2017.206. Epub 2017 Jul 6.

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

Author information

1
MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA.
2
Bristol-Myers Squibb Company, PO Box 5400, J42-05, Princeton, NJ 08543, USA.
3
Pfizer Translational Oncology, 10646 Science Center Dr, San Diego, CA 92121, USA.
4
Cedars-Sinai Medical Center, Samuel Oschin Comprehensive Cancer Institute, Los Angeles, CA 90048, USA.
5
US Oncology/McKesson Specialty Health, The Woodlands, TX, USA.
6
Texas Oncology, Dallas, TX, USA.
7
Baylor Sammons Cancer Center, Dallas, TX 75246, USA.
8
Novartis Pharmaceuticals Corporation, East Hanover, NJ 07936, USA.
9
Department of Medical Oncology, San Camillo and Forlanini Hospitals, Rome 00152, Italy.
10
Adaptimmune LLC, Philadelphia, PA 19112, USA.

Abstract

BACKGROUND:

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.

METHODS:

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).

RESULTS:

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.

CONCLUSIONS:

A prognostic model incorporating osteopontin, interleukin-6, TIMP-1, tumour burden, and selected clinical criteria increased prognostic accuracy for OS determination in mRCC patients.

PMID:
28683470
PMCID:
PMC5558688
DOI:
10.1038/bjc.2017.206
[Indexed for MEDLINE]
Free PMC Article

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