A new study provides evidence that a prostate cancer vaccine combined with hormone-deprivation therapy can help patients with recurrent prostate cancer. The results of this clinical trial, led by scientists at the National Cancer Institute (NCI), appear in the August Journal of Urology.

The phase II trial was designed to treat patients with nonmetastatic prostate cancer who were experiencing rising levels of prostate-specific antigen (PSA), an indicator of disease recurrence. Prostate cancer often progresses several years after treatment with hormone-deprivation (antiandrogen) therapy.

This is the first study to combine antiandrogen therapy and a cancer vaccine for treating prostate cancer, and also the first randomized clinical trial in this population of prostate cancer patients.

"The question is, what do you do for someone who has already failed standard therapy with hormones?" said Dr. Philip M. Arlen of the Laboratory of Tumor Immunology and Biology in NCI's Center for Cancer Research (CCR) and first author on the study. "This study was designed to help answer that question and examined a population of patients whose cancers were resistant to hormone therapy and had no metastatic disease that was observable by computed tomography scan, but had a rising PSA score."

NCI scientists randomly assigned 42 prostate cancer patients to receive either vaccine or second-line antiandrogen treatment with the hormone nilutamide. After the first 6 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. The CCR scientists worked with a vaccine jointly developed under a Collaborative Research and Development Agreement with Therion Biologics Corp.

There were no serious side effects from the vaccine, but three of the participants receiving nilutamide experienced severe toxic reactions. Median time from treatment initiation to failure - defined as either rising PSA levels, metastases, or serious toxicity - was 9.9 months for patients who received vaccine alone compared with 7.6 months for those on nilutamide alone. However, 12 of the 21 vaccine recipients had nilutamide added to their treatment regimens after 6 months. 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 with vaccine "may be because the vaccine acts to 'prime' the immune system, and when you add the hormone treatment, it allows the vaccine to work even better," explained Dr. Arlen. "Our study indicates there may well be a synergy between immunotherapy with vaccines and hormone deprivation. However, only a larger phase III study can prove this point."

Dr. Arlen and his team are planning a new study using a vaccine and antiandrogen therapy at the same time, instead of sequentially, in similar patients. They will test a newer, more potent prostate cancer vaccine in the next study. The researchers also will use a different hormone treatment 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," Dr. 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."

By Bill Robinson