title: Phase I clinical trial of an adenovirus/prostate-specific antigen vaccine for prostate cancer: safety and immunologic results.
abstract: OBJECTIVE
  We performed a phase I clinical trial of adenovirus/prostate-specific antigen (PSA) vaccine in men with measurable metastatic hormone-refractory disease.
  
  
  METHODS
  Men with measurable metastatic disease received one vaccine injection. Toxicity, immune responses, changes in PSA doubling times, and patient survival were assessed. Thirty-two patients with hormone-refractory metastatic prostate cancer were treated with a single s.c. vaccine injection at one of three dose levels, either as an aqueous solution or suspended in a Gelfoam matrix. All patients returned for physical and clinical chemistry examinations at regular intervals up to 12 months after injections.
  
  
  RESULTS
  The vaccine was deemed safe at all doses in both administration forms. There were no serious vaccine-related adverse events; the most prevalent were localized erythema/ecchymoses and cold/flu-like symptoms. Anti-PSA antibodies were produced by 34% of patients and anti-PSA T-cell responses were produced by 68%. PSA doubling time was increased in 48%, whereas 55% survived longer than predicted by the Halabi nomogram.
  
  
  CONCLUSIONS
  The adenovirus/PSA vaccine was proven safe with no serious vaccine-related adverse events. The majority of vaccinated patients produced anti-PSA T-cell responses and over half survived longer than predicted by nomogram. Although the latter data are only derived from a small number of patients in this phase I trial, they are encouraging enough to pursue further studies.
authors.affiliation: Department of Urology, University of Iowa, Iowa City, Iowa 52242, USA. david-lubaroff@uiowa.edu
authors.forename: David M
authors.initials: DM
authors.lastname: Lubaroff
authors.forename: Badrinath R
authors.initials: BR
authors.lastname: Konety
authors.forename: Brian
authors.initials: B
authors.lastname: Link
authors.forename: Jack
authors.initials: J
authors.lastname: Gerstbrein
authors.forename: Tammy
authors.initials: T
authors.lastname: Madsen
authors.forename: Mary
authors.initials: M
authors.lastname: Shannon
authors.forename: Jeanne
authors.initials: J
authors.lastname: Howard
authors.forename: Jennifer
authors.initials: J
authors.lastname: Paisley
authors.forename: Diana
authors.initials: D
authors.lastname: Boeglin
authors.forename: Timothy L
authors.initials: TL
authors.lastname: Ratliff
authors.forename: Richard D
authors.initials: RD
authors.lastname: Williams
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000368:Aged; D000369:Aged, 80 and over; D019496:Cancer Vaccines / Q000627:therapeutic use*; D003094:Collagen / Q000737:chemistry; D005781:Gelatin Sponge, Absorbable / Q000737:chemistry; D006728:Hormones / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D017430:Prostate-Specific Antigen / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000628:therapy*; D013601:T-Lymphocytes / Q000378:metabolism
chemical_list: D019496:Cancer Vaccines; D006728:Hormones; D003094:Collagen; D017430:Prostate-Specific Antigen