title: Phase II study of the human anti-epithelial cell adhesion molecule antibody adecatumumab in prostate cancer patients with increasing serum levels of prostate-specific antigen after radical prostatectomy.
abstract: BACKGROUND
  Rising serum levels of prostate-specific antigen (PSA) after radical prostatectomy are indicative of recurrent prostate cancer. This double-blind, placebo-controlled phase II study evaluated the anti-tumour activity of the anti-epithelial cell adhesion molecule (EpCAM) antibody adecatumumab in delaying biochemical disease progression.
  
  
  METHODS
  Prostate cancer patients with increasing serum PSA levels following radical prostatectomy were randomized to low- (2 mg/kg) or high-dose adecatumumab (6 mg/kg) or placebo. The primary efficacy endpoint was the mean change from baseline in total serum PSA at week 24. Secondary endpoints included PSA response rate, prolongation of serum PSA doubling time and time to biochemical disease progression.
  
  
  RESULTS
  The primary and secondary endpoints of the study were not met in the predefined analyses. In a retrospective analysis of patients with baseline PSA ≤ 1 ng/ml and a high EpCAM expression, both the mean increase in PSA from baseline to week 24 and the PSA doubling time at week 15 were significantly improved in the high-dose adecatumumab group compared with the placebo group. Most frequent treatment-related clinical adverse events were gastrointestinal (diarrhoea and nausea) or general events (chills), showing a dose dependency but no grade 3/4 intensity in any patient.
  
  
  CONCLUSIONS
  In men with rising PSA levels after radical prostatectomy and no evidence of clinical relapse, adecatumumab delayed disease progression in a subgroup of patients with baseline PSA levels ≤ 1 ng/ml and high EpCAM-expressing tumours.
authors.affiliation: Practice for Oncology and Hematology, Freiburg, Germany.
authors.forename: Norbert
authors.initials: N
authors.lastname: Marschner
authors.forename: Dominik
authors.initials: D
authors.lastname: Rüttinger
authors.forename: Gerhard
authors.initials: G
authors.lastname: Zugmaier
authors.forename: Gyula
authors.initials: G
authors.lastname: Nemere
authors.forename: Jan
authors.initials: J
authors.lastname: Lehmann
authors.forename: Peter
authors.initials: P
authors.lastname: Obrist
authors.forename: Patrick A
authors.initials: PA
authors.lastname: Baeuerle
authors.forename: Andreas
authors.initials: A
authors.lastname: Wolf
authors.forename: Margit
authors.initials: M
authors.lastname: Schmidt
authors.forename: Per-Anders
authors.initials: PA
authors.lastname: Abrahamsson
authors.forename: Carsten
authors.initials: C
authors.lastname: Reinhardt
authors.forename: Axel
authors.initials: A
authors.lastname: Heidenreich
mesh_terms: D000368:Aged; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000951:Antigens, Neoplasm / Q000276:immunology; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D015815:Cell Adhesion Molecules / Q000009:adverse effects / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004311:Double-Blind Method; D000071858:Epithelial Cell Adhesion Molecule; D005060:Europe; D006801:Humans; D008297:Male; D008875:Middle Aged; D015990:Placebo Effect; D017430:Prostate-Specific Antigen / Q000097:blood*; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000276:immunology / Q000601:surgery*; D012189:Retrospective Studies; D013997:Time Factors; D016896:Treatment Outcome; D015854:Up-Regulation
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D015815:Cell Adhesion Molecules; C499379:EPCAM protein, human; D000071858:Epithelial Cell Adhesion Molecule; C460839:adecatumumab; D017430:Prostate-Specific Antigen