PURPOSE: Interleukin-6 (IL-6) has emerged as a key factor in the pathogenesis of 
the atypical lymphoproliferative disorder Castleman's disease (CD). Siltuximab 
is a new anti-IL-6, chimeric monoclonal antibody with potential therapeutic 
benefit in patients with CD.
METHODS: We report interim results from an open-label, dose-finding, 
seven-cohort, phase I study in which patients with symptomatic, multicentric or 
unresectable, unicentric CD received siltuximab at 1-, 2-, or 3-week intervals. 
The main efficacy end point of clinical benefit response (CBR) was defined as a 
composite of clinical and laboratory measures relevant to the management of CD. 
In addition, radiologic response was independently assessed by using modified 
Cheson criteria.
RESULTS: Eighteen (78%) of 23 patients (95% CI, 56% to 93%) achieved CBR, and 12 
patients (52%) demonstrated objective tumor response. All 11 patients (95% CI, 
72% to 100%) treated with the highest dose of 12 mg/kg achieved CBR, and eight 
patients (73%) achieved objective tumor response. Overall objective-response 
duration ranged from 44 to > or = 889 days, and one patient had complete 
response for > or = 318 days. Hemoglobin increased markedly in 19 patients 
(median increase, 2.1 g/dL; range, 0.2 to 4.7 g/dL) in the absence of 
transfusion or erythropoiesis-stimulating agents. No dose-limiting toxicity was 
reported, and only three patients had grade 3 or higher adverse events after a 
median exposure of 331 days (range, 1 to 1,148 days).
CONCLUSION: These interim results strongly suggest that siltuximab is an 
effective treatment with favorable safety for the management of CD. An 
additional study is planned to fully evaluate safety and efficacy at the 
recommended dose of 12 mg/kg every 3 weeks.