title: A national multicenter phase 2 study of prostate-specific antigen (PSA) pox virus vaccine with sequential androgen ablation therapy in patients with PSA progression: ECOG 9802.
abstract: BACKGROUND
  E9802 was a phase 2 multi-institution study conducted to evaluate the safety and effectiveness of vaccinia and fowlpox prostate-specific antigen (PSA) vaccine (step 1) followed by combination with androgen ablation therapy (step 2) in patients with PSA progression without visible metastasis.
  
  
  OBJECTIVE
  To test the hypothesis that vaccine therapy in this early disease setting will be safe and have a biochemical effect that would support future studies of immunotherapy in patients with minimal disease burden.
  
  
  METHODS
  Patients who had PSA progression following local therapy were treated with PROSTVAC-V (vaccinia)/TRICOM on cycle 1 followed by PROSTVAC-F (fowlpox)/TRICOM for subsequent cycles in combination with granulocyte-macrophage colony-stimulating factor (step 1). Androgen ablation was added on progression (step 2).
  
  
  METHODS
  Step 1 primary end points included progression at 6 mo and characterization of change in PSA velocity pretreatment to post-treatment. Step 2 end points included PSA response with combined vaccine and androgen ablation.
  
  
  CONCLUSIONS
  In step 1, 25 of 40 eligible patients (63%) were progression free at 6 mo after registration (90% confidence interval [CI], 48-75). The median pretreatment PSA velocity was 0.13 log(PSA)/mo, in contrast to median postregistration velocity of 0.09 log(PSA)/mo (p=0.02), which is an increase in median PSA doubling time from 5.3 mo to 7.7 mo. No grade ≥4 treatment-related toxicity was observed. In the 27 patients eligible and treated for step 2, 20 patients achieved a complete response (CR) at 7 mo (CR rate: 74%; 90% CI, 57-87). Although supportive of larger studies in the cooperative group setting, this study is limited by the small number of patients and the absence of a control group as in a phase 3 study.
  
  
  CONCLUSIONS
  A viral PSA vaccine can be administered safely in the multi-institutional cooperative group setting to patients with minimal disease volume alone and combined with androgen ablation, supporting the feasibility of future phase 3 studies in this population.
  
  
  RESULTS
  These data support consideration of vaccine therapy earlier in the course of prostate cancer progression with minimal disease burden in future studies of vaccine approaches in earlier stages of disease.
authors.affiliation: Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA. Electronic address: Robert.DiPaola@rutgers.edu.
authors.forename: Robert S
authors.initials: RS
authors.lastname: DiPaola
authors.affiliation: Dana-Farber Cancer Institute, Boston, MA, USA.
authors.forename: Yu-Hui
authors.initials: YH
authors.lastname: Chen
authors.affiliation: Beth Israel Deaconess Medical Center, Boston, MA, USA.
authors.forename: Glenn J
authors.initials: GJ
authors.lastname: Bubley
authors.affiliation: Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA.
authors.forename: Mark N
authors.initials: MN
authors.lastname: Stein
authors.affiliation: Indiana University Simon Cancer Center, Indianapolis, IN, USA.
authors.forename: Noah M
authors.initials: NM
authors.lastname: Hahn
authors.affiliation: Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Carducci
authors.affiliation: Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA.
authors.forename: Edmund C
authors.initials: EC
authors.lastname: Lattime
authors.affiliation: National Cancer Institute, Bethesda, MD, USA.
authors.forename: James L
authors.initials: JL
authors.lastname: Gulley
authors.affiliation: National Cancer Institute, Bethesda, MD, USA.
authors.forename: Philip M
authors.initials: PM
authors.lastname: Arlen
authors.affiliation: University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Lisa H
authors.initials: LH
authors.lastname: Butterfield
authors.affiliation: UW Carbone Cancer Center, University of Wisconsin, Madison, WI, USA.
authors.forename: George
authors.initials: G
authors.lastname: Wilding
mesh_terms: D000368:Aged; D000726:Androgen Antagonists / Q000627:therapeutic use*; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D018450:Disease Progression; D005587:Fowlpox virus / Q000276:immunology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use; D006801:Humans; D007610:Kallikreins / Q000097:blood / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D017430:Prostate-Specific Antigen / Q000097:blood / Q000276:immunology*; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D014616:Vaccinia virus / Q000276:immunology
chemical_list: D000726:Androgen Antagonists; D019496:Cancer Vaccines; C588274:PROSTVAC; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; C549870:KLK3 protein, human; D007610:Kallikreins; D017430:Prostate-Specific Antigen
keywords: PSA; Pox virus; Prostate cancer; Vaccine