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Interleukin-6, Interleukin-10, and Vascular Endothelial Growth Factor in Metastatic Renal Cell Carcinoma: Prognostic Value of Interleukin-6—From the Groupe Français d'Immunothérapie

From the Cytokines and Cancer Research Unit, INSERM U.590, Medical Oncology Department, and Public Health Department, Centre Léon Bérard; Hôpital Edouard Herriot, Lyon; Institut Gustave Roussy, Villejuif; Institut Bergonié, Bordeaux; Centre Gauducheau, Nantes Saint-Herblain; Centre Claudius Régaud, Toulouse, France

Address reprint requests to Sylvie Négrier, MD, Cytokines and Cancer Research Unit, INSERM U.590 & Medical Oncology Department, Centre Léon Bérard, 69373 Lyon Cedex 08, France; e-mail: negrier{at}lyon.fnclcc.fr

PURPOSE: Few clinical prognostic factors have been identified for patients with metastatic renal cell carcinoma (MRCC), and no biomarker is known in this disease. Several endogenous cytokines have demonstrated interesting and significant correlations with survival in these patients. Our objective was to analyze the prognostic value of circulating vascular endothelial growth factor (VEGF), interleukin-10 (IL-10), and interleukin-6 (IL-6).

PATIENTS AND METHODS: Serum levels of IL-6, IL-10, and VEGF were measured in patients with MRCC. Their prognostic value for response to treatment and progression-free and overall survival was evaluated. Pretreatment samples were obtained from 138 patients of a large randomized multicentric trial. Endogenous cytokine levels were determined using immunoassays. Univariate and multivariate analyses were performed to evaluate the prognostic value of each factor further controlled by an internal validation test. Threshold values for serum IL-6 and VEGF were determined using the quartile method.

RESULTS: Serum IL-6 was detectable in 70% of the patients. IL-10 and VEGF were elevated in 8% and 71% of the patients, respectively. None of these circulating factors was correlated with response to treatment. IL-10 was not significantly correlated with progression-free or overall survival. Despite significant correlation with survival, VEGF was not an independent prognostic factor in the multivariate analysis. Finally, IL-6 was significantly correlated with progression-free survival and overall survival, and has prognostic value for overall survival.

CONCLUSION: Circulating IL-6 level appears to be an important independent prognostic factor in patients with MRCC; if confirmed in further studies, it could be considered for treatment decisions in these patients.

Supported by a grant from the Comité de Saône et Loire of the French Ligue Nationale contre le Cancer.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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