title: Antiandrogen, vaccine and combination therapy in patients with nonmetastatic hormone refractory prostate cancer.
abstract: OBJECTIVE
  There is no current standard treatment for patients with prostate cancer who have received hormonal therapy but have an increasing prostate specific antigen (PSA) without radiographic evidence of metastasis. This trial was designed to analyze toxicity, immunogenicity and time to treatment failure using vaccine, antiandrogen therapy or their sequential use.
  
  
  METHODS
  A total of 42 patients were randomized to receive vaccine vs antiandrogen therapy with nilutamide. The vaccine consisted of recombinant vaccinia viruses containing the PSA and B7.1 costimulatory genes as prime vaccinations, and avipox-PSA as boosters. After 6 months patients with an increasing PSA and no metastasis may receive a combination of both treatments.
  
  
  RESULTS
  Three patients on nilutamide were removed from study secondary to grade 3 toxicities but no grade 3 toxicities were attributed to vaccine. In the vaccine arm median time to treatment failure was 9.9 months with 13 of 21 decreases in PSA velocity vs 7.6 months with 16 of 21 decreases in PSA velocity in the nilutamide arm (p =0.28). Of the patients in the nilutamide arm 8 had vaccine added at the time of PSA progression. Median time to treatment failure with combined therapy was 5.2 months, with a median duration from study entry of 15.9 months. Of the patients in the vaccine arm 12 had nilutamide added at the time of PSA progression. Median time to treatment failure with combined therapy was 13.9 months and a median of 25.9 months from initiation of therapy.
  
  
  CONCLUSIONS
  Further studies are merited to investigate the role of combining vaccine with antiandrogen therapy or vaccine followed by vaccine plus antiandrogen therapy in this patient population.
authors: Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors: Philip M
authors: PM
authors: Arlen
authors: James L
authors: JL
authors: Gulley
authors: Nushin
authors: N
authors: Todd
authors: Ronald
authors: R
authors: Lieberman
authors: Seth M
authors: SM
authors: Steinberg
authors: Steve
authors: S
authors: Morin
authors: Anne
authors: A
authors: Bastian
authors: Jennifer
authors: J
authors: Marte
authors: Kwong-Yok
authors: KY
authors: Tsang
authors: Patricia
authors: P
authors: Beetham
authors: Douglas W
authors: DW
authors: Grosenbach
authors: Jeffrey
authors: J
authors: Schlom
authors: William
authors: W
authors: Dahut
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000726:Androgen Antagonists / Q000627:therapeutic use*; D019496:Cancer Vaccines / Q000737:chemistry / Q000627:therapeutic use*; D018450:Disease Progression; D006801:Humans; D048289:Imidazolidines / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000401:mortality / Q000628:therapy*
chemical_list: D000726:Androgen Antagonists; D019496:Cancer Vaccines; D048289:Imidazolidines; C021277:nilutamide; D017430:Prostate-Specific Antigen