title: Randomized trial of autologous cellular immunotherapy with sipuleucel-T in androgen-dependent prostate cancer.
abstract: OBJECTIVE
  Sipuleucel-T, an autologous cellular immunotherapy, was investigated in a randomized, double-blind, controlled trial to determine its biologic activity in androgen-dependent prostate cancer (ADPC).
  
  
  METHODS
  Patients with prostate cancer detectable by serum prostate-specific antigen (PSA) following radical prostatectomy received 3 to 4 months of androgen suppression therapy, and were then randomized (2:1) to receive sipuleucel-T (n = 117) or control (n = 59). The primary endpoint was time to biochemical failure (BF) defined as serum PSA ≥ 3.0 ng/mL. PSA doubling time (PSADT), time to distant failure, immune response, and safety were also evaluated.
  
  
  RESULTS
  Median time to BF was 18.0 months for sipuleucel-T and 15.4 months for control (HR = 0.936, P = 0.737). Sipuleucel-T patients had a 48% increase in PSADT following testosterone recovery (155 vs. 105 days, P = 0.038). With only 16% of patients having developed distant failure, the treatment effect favored sipuleucel-T (HR = 0.728, P = 0.421). The most frequent adverse events in sipuleucel-T patients were fatigue, chills, and pyrexia. Immune responses to the immunizing antigen were greater in sipuleucel-T patients at Weeks 4 and 13 (P < 0.001, all) and were sustained prior to boosting as measured in a subset of patients a median of 22.6 months (range: 14.3-67.3 months) following randomization.
  
  
  CONCLUSIONS
  No significant difference in time to BF could be shown. The finding of increased PSADT in the sipuleucel-T arm is consistent with its biologic activity in ADPC. Long-term follow-up will be necessary to determine if clinically important events, such as distant failure, are affected by therapy. Treatment was generally well tolerated.
authors.affiliation: Oregon Health & Science University Knight Cancer Institute, Portland, Oregon, USA. beert@ohsu.edu
authors.forename: Tomasz M
authors.initials: TM
authors.lastname: Beer
authors.forename: Guy T
authors.initials: GT
authors.lastname: Bernstein
authors.forename: John M
authors.initials: JM
authors.lastname: Corman
authors.forename: L Michael
authors.initials: LM
authors.lastname: Glode
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Hall
authors.forename: Wayne L
authors.initials: WL
authors.lastname: Poll
authors.forename: Paul F
authors.initials: PF
authors.lastname: Schellhammer
authors.forename: Lori A
authors.initials: LA
authors.lastname: Jones
authors.forename: Yi
authors.initials: Y
authors.lastname: Xu
authors.forename: Jelle W
authors.initials: JW
authors.lastname: Kylstra
authors.forename: Mark W
authors.initials: MW
authors.lastname: Frohlich
mesh_terms: D000368:Aged; D000728:Androgens / Q000378:metabolism*; D019496:Cancer Vaccines / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000009:adverse effects; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D017430:Prostate-Specific Antigen / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000276:immunology / Q000628:therapy*; D014020:Tissue Extracts / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D015854:Up-Regulation / Q000276:immunology
chemical_list: D000728:Androgens; D019496:Cancer Vaccines; D014020:Tissue Extracts; D018799:Intercellular Adhesion Molecule-1; C511774:sipuleucel-T; D017430:Prostate-Specific Antigen