BETHESDA, Md.—Giving patients a continuous, low dose of vaccine therapy is not only better tolerated by most patients compared to standard vaccine administration methods, but it may also help further the development of vaccine therapies for prostate cancer, according to a recent
National Cancer Institute (NCI) study.
An alternative vaccine strategy known as metronomic dosing is safe and produces similar immune responses and fewer side effects than traditional dosing methods, which are not well tolerated by most patients, the NCI wrote in the study, published Aug. 15 in the
American Association for Cancer Research journal
Clinical Cancer Research. Traditional vaccine methods usually combine immune system boosters such as IL-2 to heighten the body's natural defenses, but they frequently cause substantial side effects such as fatigue and high blood sugar.
In this new study, the NCI researchers sought to decrease the side effects associated with IL-2 by treating 18 patients with the vaccine and radiation therapy, but with lower doses of IL-2 given over a longer period of time. The vaccine used by the NCI was designed to stimulate an immune response against prostate-specific antigen (PSA), a protein produced by the prostate that is often found at elevated levels in the blood of men who have prostate cancer and some non-cancerous prostate conditions.
With metronomic dosing, less than a quarter of the patients had side effects that required their dose of IL-2 to be reduced. The researchers also noted that, similar to the standard dosing method, metronomic dosing of IL-2 induced immune responses against other prostate cancer antigens in some patients.
"This study showed that giving a different dose and schedule of IL-2 appeared to produce a similar immune response, but was much better tolerated," says Dr. James L. Gulley, of NCI's
Center for Cancer Research. "This improved tolerability may enable us to use IL-2 in other vaccine strategies. The vaccine is designed to produce tumor-specific T-cells, and IL-2 is an important growth factor for these T-cells."
Gulley says he hopes the findings will give clinical researchers another modality to combine with vaccine platforms that will be well tolerated and have the potential to improve immunologic activity, improving patient outlook. However, more research is needed to evaluate the efficacy of this dosing method in treating prostate cancer, he cautions.
"The next step is really to do a trial designed to see if this strategy can be used to decrease the likelihood of prostate cancer recurrence following radiation therapy," he says. "Unfortunately, PSA rises in 30 to 40 percent of patients, depending on an individual patient's disease characteristics, following local therapy. This is too high. It would be exceptionally rewarding to make an impact in this number, especially since this year 186,320 men in the US are expected to be diagnosed with this disease and one in six men in the United States will be diagnosed during their lifetime."
