Combination Hormone/Vaccine Therapy For Prostate Cancer May Benefit Patients Whose Disease Returns

This phase II trial (a trial that usually tests the effectiveness of a drug) was designed to treat patients with nonmetastatic prostate cancer who were experiencing rising levels of prostate-specific antigen (PSA), which can indicate recurrence of the disease. Prostate cancer often progresses several years after treatment with hormone-deprivation therapy .

This is the first study to combine antiandrogen therapy (reducing the amount 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."

NCI scientists randomly assigned 42 prostate cancer patients to receive either vaccine or second-line antiandrogen treatment, which consisted of the hormone nilutamide. Nilutamide works by blocking the effects of excess testosterone, a hormone produced by the body that can promote the growth of cancer cells. 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.

There were no serious side effects from the vaccine, but some of the participants receiving nilutamide experienced severe adverse reactions involving lung toxicities, an uncommon side effect sometimes associated with the drug. 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 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," 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."

For more information about cancer, visit the NCI Web site at http://www.cancer.gov or call NCI's Cancer Information Service at 1-800-4 CANCER (1-800-422-6237).

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* Arlen PM , Gulley, JL, Todd N, Lieberman R, Steinberg SM, Morin S, Bastian A, Marte J, Tsang K, Beetham P, Grosenbach DW, Schlom J, Dahut W. Antiandrogen, vaccine and combination therapy in patients with nonmetastatic hormone refractory prostate cancer. Journal of Urology. August 2005.