PSA Rising, July 25, 2005.-- A prostate cancer vaccine given before secondline hormone therapy may improve results for some prostate cancer patients.
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.
In a study of hormone-refractory patients, those who received a vaccine before a secondline hormone therapy had a median of 13.9 disease-free months, compared with 7.6 months for those who received hormone therapy only, reported Philip M. Arlen, M.D., and colleagues at the National Cancer Institute.
The vaccine in this study consisted of a recombinant vaccinia virus containing the human genes for prostate-specific antigen and rV-B7.1.
When the study was completed, three patients who had received Anandron had been removed from the study due to moderate side effects. No significant side effects were observed among the patients treated with vaccine.
The results suggest that "the vaccine acts to 'prime' the immune system, and when you add the hormone treatment, it allowed the vaccine to work even better," said Dr. Arlen, whose study was published online today by The Journal of Urology.
The phase II study included 42 prostate cancer patients who had received first-line hormonal therapy but still showed increasing prostate-specific antigen levels. None of the patients had radiographic evidence of metastasis.
The patients were randomly assigned to either a recombinant prostate cancer vaccine or Nilandron (nilutamide), a second-line hormone therapy, for six months. After six months, patients could choose to receive a combination of both treatments. Follow-up was about four years, and the main outcome measure was time to treatment failure.
Neither the vaccine nor hormone therapy alone appeared to have a significant effect. Median time to treatment failure was 9.9 months for the vaccine group versus 7.6 months for the hormone therapy group (P=0.28).
Receiving the vaccine after hormone therapy also appeared to have little effect. Median time to treatment failure in this group was 5.2 months.
However, for the group who received the vaccine before hormone therapy, median time to treatment failure was 13.9 months, for a total of 25.9 months from the beginning of their treatments (probability rank not reported).
"Our study indicates there may well be a synergy between immunotherapy with vaccines and hormone deprivation," Dr. Arlen said.
New and more potent vaccines have now entered phase I trials. In view of the minimal toxicity and the possible synergy between vaccine and hormone therapy observed in this study, the authors believe that further prostate cancer vaccine studies are warranted. "Our goal moving forward is to introduce the vaccine into earlier treatment stages."
Patients' responses
In more detail, 62% of patients in the vaccine group and 76% of patients in the Anandron group had decreases in PSA velocity with initial therapy. After six months, eight of the patients in the Anandron group had vaccine added to treatment which resulted in treatment failure in 5.2 months. Patients receiving Anandron followed by vaccine had a median time on study of 15.9 months. Twelve patients in the vaccine group received Anandron with a median time to progression of 13.9 months and had a median of 25.9 months of therapy. It appeared from this preliminary study that combined vaccine and anti-androgen therapy was the most effective approach for future studies.
This approach to treating prostate cancer is still in the preliminary, investigative stages and is only available in the context of a clinical trial.
"Further studies are merited," the researchers conclude, 'to investigate the role of combining vaccine with antiandrogen therapy or vaccine followed by vaccine plus antiandrogen therapy in this patient population.
Other vaccines under testing for prostate cancer include Dendreon's Provenge vaccine and the G-VAX vaccine.
