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Annals of Oncology Advance Access published online on June 18, 2009
Annals of Oncology, doi:10.1093/annonc/mdp054
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© The Author 2009. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org

Cytokines and angiogenic factors in patients with metastatic renal cell carcinoma treated with interferon-{alpha}: association of pretreatment serum levels with survival

A. J. Montero1,{dagger},{ddagger}, C. M. Diaz-Montero2,{dagger},{ddagger}, R. E. Millikan1,*, J. Liu3, K.-A. Do3, S. Hodges1, E. Jonasch1, B. W. McIntyre2, P. Hwu4 and N. Tannir1

1 Department of Genitourinary Medical Oncology
2 Department of Immunology
3 Department of Biostatistics and Applied Mathematics
4 Department of Melanoma, University of Texas MD Anderson Cancer Center, Houston, TX, USA

* Correspondence to: Dr R. Millikan, Department of Genitourinary Medical Oncology, University of Texas MD Anderson Cancer Center, Unit 1374, 1155 Pressler Boulevard, Houston, TX 77030, USA. Tel: +1-713-792-2830; Fax: +1-713- 745-1625; E-mail: remillika{at}mdanderson.org

Background: To correlate serum cytokine and angiogenic factor (CAF) levels with overall survival (OS) in metastatic renal cell carcinoma (mRCC) treated with interferon-{alpha} (IFN-{alpha}).

Patients and methods: Serum CAF levels were measured in 103 patients treated on a randomized trial with IFN-{alpha} 0.5 million units (MU) twice daily or 5 MU daily. Concentrations of 17 analytes were determined by multiplex bead immunoassays [vascular endothelial growth factor A (VEGFA) and several cytokines] or enzyme-linked immunosorbent assay (basic fibroblast growth factor). We used proportional hazards models to evaluate the effect of CAF levels and clinical factors on OS.

Results: Pretreatment serum interleukin (IL) 5, IL-12 p40, VEGFA, and IL-6 levels and Memorial Sloan-Kettering Cancer Center risk grouping independently correlated with OS, with hazard ratios of 2.33, 2.00, 2.07, 1.82, and 0.39, respectively (concordance index = 0.69 for the combined model versus 0.60 for the CAF model versus 0.52 for the clinical model). Based on an index derived from these five risk factors (RFs), patients with 0–2 RF had a median OS time of 32 months versus 9 months for patients with 3–5 RF (P < 0.0001).

Conclusions: Serum CAF profiling contributes to prognostic evaluation in mRCC and helps to identify a subset of patients with 20% 5-year OS.

angiogenesis, cytokine profiling, inflammation, interferon-{alpha}, metastatic renal cell carcinoma, multiplex bead immunoassays

{dagger} Both authors contributed equally.

{ddagger} Present address: Department of Internal Medicine, University of Miami Sylvester Comprehensive Cancer Center, Miami, FL, USA.

Received for publication November 18, 2008. Revision received February 5, 2009. Accepted for publication February 11, 2009.


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