title: A randomized, double-blind, multicenter, phase 2 study of a human monoclonal antibody to human αν integrins (intetumumab) in combination with docetaxel and prednisone for the first-line treatment of patients with metastatic castration-resistant prostate cancer.
abstract: BACKGROUND
  Intetumumab is a fully human mAb with antiangiogenic, antitumor properties which has shown potential therapeutic effect in castration-resistant prostate cancer (CRPC) patients.
  
  
  METHODS
  In a phase 2, randomized, double-blind, multicenter study, men with metastatic CRPC without prior systemic nonhormonal therapy were randomly assigned to 75-mg/m(2) docetaxel (Taxotere) and 5-mg prednisone plus placebo (N = 65) or 10-mg/kg intetumumab (N = 66) q3w. Placebo patients with progressive disease (PD) could cross over to 10-mg/kg intetumumab alone or with docetaxel. The primary end-point was progression-free survival (PFS). The secondary end-points included tumor response (complete response + partial response, CR + PR), prostate-specific antigen (PSA) response, and overall survival (OS).
  
  
  RESULTS
  All efficacy end-points favored placebo over intetumumab, including PFS (median 11.0 versus 7.6 months, P = 0.014), tumor response (20% versus 16%, P = 0.795), PSA response (68% versus 47%, P = 0.018), OS (median 20.6 versus 17.2 months, P = 0.163). Common all-grade adverse events (AEs) with placebo and intetumumab were alopecia (43% versus 26%); diarrhea, leukopenia (both 34% versus 27%); neutropenia (35% versus 23%). Grade ≥ 3 leukopenia (28% versus 17%) and neutropenia (26% versus 18%) occurred more often with placebo than with intetumumab. Intetumumab serum concentrations increased with repeated dosing and did not reach steady-state. Greater decreases in N-telopeptide of type I collagen (NTx), C-telopeptide (CTx) and CTCs occurred with intetumumab than with placebo.
  
  
  CONCLUSIONS
  The addition of intetumumab to docetaxel resulted in shorter PFS without additional toxicity among CRPC patients.
authors.affiliation: Department of Urology, University Hospital of Cologne, Cologne. Electronic address: aheidenreich@ukaachen.de.
authors.forename: A
authors.initials: A
authors.lastname: Heidenreich
authors.affiliation: Department of Uro-Oncology, Rajiv Gandhi Cancer Institute and Research Centre, New Delhi, India.
authors.forename: S K
authors.initials: SK
authors.lastname: Rawal
authors.affiliation: Urological Ward, Koscierzyna Hospital, Koscierzyna, Poland.
authors.forename: K
authors.initials: K
authors.lastname: Szkarlat
authors.affiliation: P. A. Hertzen Oncology Research Institute, Moscow, Russia.
authors.forename: N
authors.initials: N
authors.lastname: Bogdanova
authors.affiliation: Department of Cancer Research, GZA Hospitals St. Augustine Campus, Wilrijk, Belgium.
authors.forename: L
authors.initials: L
authors.lastname: Dirix
authors.affiliation: Department of Urology, Eberhard-Karls University, Tübingen.
authors.forename: A
authors.initials: A
authors.lastname: Stenzl
authors.affiliation: Hematology/Oncology, Studienzentrum, Aschaffenburg, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Welslau
authors.affiliation: Biostatistics, Janssen Research & Development, Spring House.
authors.forename: G
authors.initials: G
authors.lastname: Wang
authors.affiliation: Hematology & Oncology General, Janssen Research & Development, Raritan, USA.
authors.forename: F
authors.initials: F
authors.lastname: Dawkins
authors.affiliation: Oncology, Janssen Biologics Europe, Leiden, The Netherlands.
authors.forename: C J
authors.initials: CJ
authors.lastname: de Boer
authors.affiliation: Medical Oncology, Hospital Network Antwerp (ZNA)-Middelheim, Antwerp, Belgium.
authors.forename: D
authors.initials: D
authors.lastname: Schrijvers
mesh_terms: D000368:Aged; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use; D018931:Antineoplastic Agents, Hormonal / Q000009:adverse effects / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D018572:Disease-Free Survival; D000077143:Docetaxel; D004311:Double-Blind Method; D006801:Humans; D039564:Integrin alphaV / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000188:drug therapy; D009919:Orchiectomy; D010919:Placebos / Q000008:administration & dosage; D011241:Prednisone / Q000009:adverse effects / Q000627:therapeutic use*; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000401:mortality; D013534:Survival; D043823:Taxoids / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D018931:Antineoplastic Agents, Hormonal; D039564:Integrin alphaV; D010919:Placebos; D043823:Taxoids; D000077143:Docetaxel; C486839:intetumumab; D011241:Prednisone