PURPOSE: Siltuximab is a chimeric, anti-interleukin-6 monoclonal antibody with 
potential therapeutic benefit in castration-resistant prostate cancer (CRPC) 
patients. We assessed the safety and tolerability of siltuximab in combination 
with docetaxel, the pharmacokinetics of docetaxel alone and with siltuximab, and 
the efficacy and pharmacodynamics of siltuximab plus docetaxel.
PATIENTS AND METHODS: In an open-label, dose-escalation, multicenter, phase 1 
study, patients with metastatic, progressive CRPC received docetaxel 75 mg/m(2) 
q3w plus siltuximab 6 mg/kg q2w (n=12), 9 mg/kg q3w (n=12), or 12 mg/kg q3w 
(n=15). Dose-limiting toxicity (DLT), PSA, and radiologic response according to 
WHO criteria were evaluated.
RESULTS: DLT was reported in 1 of 11 patients receiving 6 mg/kg, 1 of 12 
receiving 9 mg/kg, and in 1 of 14 receiving 12 mg/kg. Common Grade ≥ 3 adverse 
events were neutropenia (73 %), leukopenia (60 %), lymphopenia (30 %), dyspnea 
(19 %), and fatigue (14 %). Toxicities were not dose dependent. Siltuximab did 
not affect docetaxel pharmacokinetics. The pharmacokinetic profile for 
siltuximab in combination was similar to single-agent siltuximab 
pharmacokinetics. Twenty-three (62 %; 95 % CI 45 %, 78 %) of 37 
combination-treated patients achieved a confirmed ≥ 50 % PSA decline. Of 17 
patients with measurable disease at baseline, 2 confirmed and 2 unconfirmed 
radiologic partial responses ranging 190 to 193 days were achieved with 9- and 
12-mg/kg siltuximab. C-reactive protein concentrations were suppressed 
throughout treatment in all patients.
CONCLUSION: These results suggest that siltuximab in combination with docetaxel 
is safe and shows preliminary efficacy in patients with CRPC, although 
alternative siltuximab schedules may be better tolerated for future studies.