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


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 (VEGF(A)) 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, VEGF(A), 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.
Montero
A J
AJ
Department of Genitourinary Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Diaz-Montero
C M
CM
Millikan
R E
RE
Liu
J
J
Do
K-A
KA
Hodges
S
S
Jonasch
E
E
McIntyre
B W
BW
Hwu
P
P
Tannir
N
N
D043925:Angiogenesis Inducing Agents / Q000097:blood / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary*; D016009:Chi-Square Distribution; D016207:Cytokines / Q000097:blood / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000097:blood; D005500:Follow-Up Studies; D006801:Humans; D007118:Immunoassay; D016898:Interferon-alpha / Q000627:therapeutic use*; D053762:Interleukin-12 Subunit p40 / Q000097:blood / Q000627:therapeutic use; D015848:Interleukin-5 / Q000097:blood / Q000627:therapeutic use; D015850:Interleukin-6 / Q000097:blood / Q000627:therapeutic use; D053208:Kaplan-Meier Estimate; D008297:Male; D016016:Proportional Hazards Models; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors; D016019:Survival Analysis; D013997:Time Factors; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000097:blood / Q000627:therapeutic use
D043925:Angiogenesis Inducing Agents; D016207:Cytokines; D016898:Interferon-alpha; D053762:Interleukin-12 Subunit p40; D015848:Interleukin-5; D015850:Interleukin-6; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2