BACKGROUND: Interleukin-6 (IL-6) is associated with prostate cancer morbidity. 
In several experimental models, IL-6 has been reported to have anti-apoptotic 
and pro-angiogenic effects. Siltuximab (CNTO 328) is a monoclonal anti-IL-6 
antibody which has been successfully applied in several models representing 
prostate cancer. This study was designed to assess preliminary safety of 
siltuximab in patients with early prostate cancer.
PATIENTS AND METHODS: Twenty patients scheduled to undergo radical prostatectomy 
received either no drug or siltuximab (6 mg/kg, five patients per group with 
administration once, two times, and three times prior to surgery). Blood samples 
were collected for pharmacokinetic and pharmacodynamic analyses. Expression of 
elements of IL-6 signaling pathways was analyzed in tumor tissue by 
immunohistochemistry. Gene analysis in tumor specimens was performed with the 
DASL array.
RESULTS: No adverse events related to siltuximab were observed. Patients treated 
with siltuximab presented with higher levels of proliferation and apoptosis 
markers. Following a single dose, serum concentrations of siltuximab declined in 
a biexponential manner. This study revealed a decrease in phosphorylation of 
Stat3 and p44/p42 mitogen-activated protein kinases. In addition, gene 
expression analyses indicate down-regulation of genes immediately downstream of 
the IL-6 signaling pathway and key enzymes of the androgen signaling pathway.
CONCLUSIONS: Preliminary safety of siltuximab is favorable. Future studies in 
which siltuximab could be combined with androgen-deprivation therapy and 
experimental therapies in advanced prostate cancer are justified.