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Fizazi K , De Bono JS , Flechon A , Heidenreich A , Voog E , Davis NB , Qi M , Bandekar R , Vermeulen JT , Cornfeld M , Hudes GR
Randomised phase II study of siltuximab (CNTO 328), an anti-IL-6 monoclonal antibody, in combination with mitoxantrone/prednisone versus mitoxantrone/prednisone alone in metastatic castration-resistant prostate cancer
European Journal of Cancer. 2012 Jan;48(1) :85-93
PMID: WOS:000299866200011   
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Abstract
Purpose: This open-label phase II trial assessed mitoxantrone/prednisone (M/P) with and without siltuximab (CNTO 328), an anti-interleukin-6 chimeric monoclonal antibody, for patients with metastatic castration-resistant prostate cancer who received prior docetaxel-based chemotherapy. Methods: Part 1 assessed the safety of biweekly siltuximab 6 mg/kg plus M 12 mg/m(2) every 3 weeks and P. Part 2 assessed efficacy and safety of siltuximab plus M/P versus M/P alone. The primary end-point was progression-free survival (PFS). Progression was defined as progressive disease per Response Evaluation Criteria in Solid Tumours (RECIST), or >= 3 new skeletal lesions with clinical deterioration or without deterioration confirmed by repeated bone scan. Rising prostate-specific antigen was not considered progression. Results: Siltuximab plus M/P was well tolerated in Part 1 (n = 9). In Part 2, 48 and 49 patients received siltuximab plus M/P or M/P alone, respectively. Enrolment was prematurely terminated by the Independent Data Monitoring Committee since an apparent imbalance in patient baseline characteristics (favoring the M/P only arm) made it unlikely that the study could achieve its primary efficacy end-point. Median PFS was 97 days with siltuximab combination and 228 days with M/P alone (hazard ratio, 1.72; P = 0.043). Use of a novel non-validated PFS definition may have contributed to this result. Abnormal laboratory assessments were more frequent with the combination. Infection and febrile neutropenia rates were similar between groups. Greater C-reactive protein suppression was achieved during siltuximab combination treatment compared with M/P alone (P = 0.0003). Conclusion: While siltuximab plus M/P appeared well tolerated, improvement in outcomes was not demonstrated. (C) 2011 Elsevier Ltd. All rights reserved.
Notes
Fizazi, K. De Bono, J. S. Flechon, A. Heidenreich, A. Voog, E. Davis, N. B. Qi, Ming Bandekar, R. Vermeulen, J. T. Cornfeld, M. Hudes, G. R. Centocor, Inc. The authors would like to thank all of the investigators and members of the Independent Data Monitoring Committee for their participation in the study. Funding for this study was provided by Centocor, Inc. Editorial support for the writing of this manuscript was provided by Nancy Bella, PharmD, of MedErgy and was funded by Centocor, Inc. 25 Elsevier sci ltd Oxford 886pl