title: 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.
abstract: OBJECTIVE
  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).
  
  
  CONCLUSIONS
  While siltuximab plus M/P appeared well tolerated, improvement in outcomes was not demonstrated.
authors: Institut Gustave Roussy, University of Paris Sud, Villejuif, France. fizazi@igr.fr
authors: K
authors: K
authors: Fizazi
authors: J S
authors: JS
authors: De Bono
authors: A
authors: A
authors: Flechon
authors: A
authors: A
authors: Heidenreich
authors: E
authors: E
authors: Voog
authors: N B
authors: NB
authors: Davis
authors: Ming
authors: M
authors: Qi
authors: R
authors: R
authors: Bandekar
authors: J T
authors: JT
authors: Vermeulen
authors: M
authors: M
authors: Cornfeld
authors: G R
authors: GR
authors: Hudes
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002277:Carcinoma / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D006801:Humans; D015850:Interleukin-6 / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage* / Q000009:adverse effects; D009362:Neoplasm Metastasis; D009919:Orchiectomy; D011241:Prednisone / Q000008:administration & dosage* / Q000009:adverse effects; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D017211:Treatment Failure; D000093242:Interleukin-6 Inhibitors
chemical_list: D000911:Antibodies, Monoclonal; D015850:Interleukin-6; D008942:Mitoxantrone; D011241:Prednisone; D000093242:Interleukin-6 Inhibitors; C504234:siltuximab