Antiandrogen, vaccine and combination therapy in patients with nonmetastatic hormone refractory prostate cancer.
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.
Arlen
Philip M
PM
Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Gulley
James L
JL
Todd
Nushin
N
Lieberman
Ronald
R
Steinberg
Seth M
SM
Morin
Steve
S
Bastian
Anne
A
Marte
Jennifer
J
Tsang
Kwong-Yok
KY
Beetham
Patricia
P
Grosenbach
Douglas W
DW
Schlom
Jeffrey
J
Dahut
William
W
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*
D000726:Androgen Antagonists; D019496:Cancer Vaccines; D048289:Imidazolidines; C021277:nilutamide; D017430:Prostate-Specific Antigen