Interleukin-6, interleukin-10, and vascular endothelial growth factor in metastatic renal cell carcinoma: prognostic value of interleukin-6--from the Groupe Francais d'Immunotherapie.
OBJECTIVE
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).


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.


CONCLUSIONS
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.
Negrier
Sylvie
S
Cytokines and Cancer Research Unit, INSERM U.590 & Medical Oncology Department, Cedex 08, France. negrier@lyon.fnclcc.fr
Perol
David
D
Menetrier-Caux
Christine
C
Escudier
Bernard
B
Pallardy
Marc
M
Ravaud
Alain
A
Douillard
Jean-Yves
JY
Chevreau
Christine
C
Lasset
Christine
C
Blay
Jean-Yves
JY
Pallardy
Michel
M
D000328:Adult; D000368:Aged; D015415:Biomarkers; D002292:Carcinoma, Renal Cell / Q000097:blood* / Q000556:secondary; D005260:Female; D006801:Humans; D016753:Interleukin-10 / Q000097:blood*; D015850:Interleukin-6 / Q000097:blood*; D007680:Kidney Neoplasms / Q000097:blood* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D015996:Survival Rate; D042442:Vascular Endothelial Growth Factors / Q000097:blood*
D015415:Biomarkers; D015850:Interleukin-6; D042442:Vascular Endothelial Growth Factors; D016753:Interleukin-10