"Our study indicates there may well be a synergy between immunotherapy with vaccines and hormone deprivation."
July 25, 2005 -- A cancer vaccine combined with hormone-deprivation therapy can help patients with recurrence of prostate cancer. This is the result of a Phase II clinical trial.
The vaccine tested consisted of recombinant vaccinia viruses containing the PSA and B7.1 costimulatory genes as prime vaccinations, and avipox-PSA as boosters.
Adding a prostate cancer vaccine to hormone therapy extended time to disease progression by nearly 14 months for men with recurrent prostate cancer compared to 9.9 months for vaccine alone and 7.6 months for hormone therapy alone.
Forty-two patients with non-metastatic prostate cancer and rising PSAs after initial treatment were randomly assigned to get androgen deprivation therapy or an experimental prostate cancer vaccine. Hormone therapy blocks the effects of the male hormone testosterone, which prostate cancer uses to grow. The experimental vaccine was designed to strengthen the patient's own immume response against the cancer.
Both therapies slowed the cancer's growth only temporarily. In the vaccine group, the median time to disease progression was 9.9 months. For the hormone therapy group, the time to progression was 7.6 months.
Hormone therapy was added to treatment for half the vaccine group. Those patients experienced an additional 13.9 months to disease progression for a total of 25.9 months from the beginning of treatment.
The NCI 's Dr. Phillip Arlen hypothesizes that hormone therapy helps the vaccine work even better in marshalling the body's defenses against the cancer.
There were no serious side effects from the vaccine although some of the patients taking hormone therapy experience severe reactions including lung toxicities.
The results of this clinical trial, led by scientists at the National Cancer Institute (NCI), part of the National Institutes of Health, appear in the August 2005 issue of the Journal of Urology .
This is the first study to combine antiandrogen therapy (to block the uptake of androgens, which are male sex hormones) and a cancer vaccine for treating prostate cancer, and also the first randomized clinical trial in this population of prostate cancer patients. Cancer vaccines are designed either to treat existing cancers or to prevent the development of cancer. The experimental vaccine used in this study was designed to strengthen the body's natural defenses against prostate cancer.
"The question is, what do you do for someone who has already failed standard therapy with hormones?" said Philip M. Arlen, M.D., of NCI's Laboratory of Tumor Immunology and Biology. "This study was designed to answer that question and examined a population of patients whose cancers were resistant to hormone therapy, had no metastatic disease that was observable by computed tomography (CT or CAT) scan, but had a rising PSA score, an indicator of recurrence."
The 42 patients were randomly assigned to receive either vaccine or second-line antiandrogen treatment, which consisted of the drug nilutamide. After the first six months of treatment, participants in both arms of the study - who had rising PSA levels but no evidence of metastatic disease - could choose to receive the other treatment in combination with their first study treatment.
Median time before the treatment started to fail was 9.9 months for individuals who received vaccine alone compared to 7.6 months for patients on nilutamide alone, a difference not considered statistically significant. However, 12 of the 21 vaccine recipients had nilutamide added to their treatment regimens after six months. The patients in that group experienced an additional median time of 13.9 months until treatment failure, for a total of 25.9 months from the beginning of their treatments.
The positive effects of combining antiandrogen therapy to vaccine "may be because the vaccine acts to 'prime' the immune system, and when you add the hormone treatment, it allowed the vaccine to work even better," explained Arlen. "Our study indicates there may well be a synergy between immunotherapy with vaccines and hormone deprivation."
The rationale for testing a vaccine/hormone therapy combination came from clinical observations showing that hormone therapy increases the number of immune cells reaching the prostate gland, thereby allowing vaccines to work more effectively.
Arlen and his NCI colleagues are planning a follow-up study using the vaccine and antiandrogen at the same time, instead of sequentially, in similar patients. They will be testing a more potent, newer prostate cancer vaccine in the next study. The NCI scientists will also use a different hormone blockade drug called Flutamide, which has fewer and less serious side effects than nilutamide.
"Our goal moving forward is to introduce the vaccines into earlier treatment stages," Arlen said. "We have shown that this therapy is safe and well-tolerated. Next we want to keep this population of patients either stable or improving, and also prevent metastatic disease. Achieving that would be a tremendous benefit in terms of their quality of life."
