15521 Background: High serum levels of pro-inflammatory cytokine IL-6 may impact the progression and survival of metastatic hormone refractory prostate cancer (HRPC). CNTO328, an anti IL-6 monoclonal antibody, inhibited prostate tumor growth in several preclinical xenograft mouse models. Methods: This Phase 1, open label study evaluates the safety, pharmacokinetics (PK), and pharmacodynamics of CNTO328 at three dose levels (6mg/kg q2 weeks, 9mg/kg q3 weeks and 12mg/kg q3 weeks) in combination with docetaxel (75mg/m2 q3 weeks) in men with metastatic HPRC. C-reactive protein (CRP), a surrogate biomarker of serum IL-6, and circulating tumor cells (CTC) are evaluated. Results: Eight patients with a median baseline PSA value of 56.8 ng/ml (range 13.6- 436.9 ng/ml) were treated in the first cohort (6 mg/kg CNTO328 q2 weeks in combination with docetaxel 75 mg/m2 q3 weeks). At baseline, 6 patients (75%) had detectable CRP and 6 patients had detectable CTCs. The median number of CNTO328 doses and docetaxel cycles administered was 6 (CNTO328: range 3 to 11 doses; docetaxel: range 3 to 13 cycles). No first-cycle DLT was observed for this combination. Three patients discontinued treatment due to docetaxel-related grade 3 adverse events (deep vein thrombosis, hyperbilirubinemia, and nail changes) after 6, 11, and 13 cycles of docetaxel, respectively. Serum CRP decreased to below detectable levels 7 days after the first dose of CNTO328 in all patients with measurable values at baseline and remained undetectable throughout treatment. Two patients with post-treatment CTC values showed CTC reduction from 82 to1, and 127 to1, respectively. Six of 8 patients had = 50% PSA reductions and all had stable or improved bone scans and/or CT scans. PK of CNTO328 and docetaxel, alone and in combination, will be presented. Conclusions: Thus far, anti-IL6 therapy with CNTO328 at 6mg/kg q2 weeks in combination with docetaxel 75mg/m2 q3 week has been feasible and tolerable. Complete suppression of CRP and PSA reduction provide evidence of biological and anti-tumor activity of this approach and support further testing. [Table: see text]
