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Vaccination Shows Promise for Extending Survival in GBM Patients

ROLLING MEADOWS, I.L. – April 25, 2006 -- Glioblastoma multiforme (GBM) is a devastating brain cancer that typically results in death in about 1 year.

These tumors tend to grow rapidly, spread to other tissue, and have a poor prognosis. They may be composed of several different kinds of cells, such as astrocytes and oligodendrocytes. GBM is more common in people ages 50 to 70 and more prevalent in men than women. Patients have few treatment options, and nearly all available therapies have had minimal impact on survival.

Researchers recently conducted a phase 2 study utilizing a therapeutic vaccine to treat GBM at MD Anderson Cancer Center and Duke Comprehensive Cancer Center. The results of this study, An Epidermal Growth Factor Receptor Variant III Peptide Vaccination Appears Promising in Newly Diagnosed GBM Patients: Preliminary Results of a Randomized Phase II Clinical Trial, will be presented by Amy B. Heimberger, MD, 11:00 to 11:15 a.m. on Tuesday, April 25, 2006, during the 74^th Annual Meeting of the American Association of Neurological Surgeons in San Francisco.

The vaccine targets the epidermal growth factor variant III (EGFRvIII), which is a tumor-specific cell surface protein expressed on approximately 30% of GBM tumors and absent in normal tissues.

EGFRvIII stimulates the growth of cancer as a result of its ability to enhance tumor proliferation, invasion, and growth of new tumor blood vessels. The peptide used in the vaccine is designed to recruit immune system defenses targeting EGFRvlll to stop or slow the growth of cancer cells. Because EGFRvIII has only rarely been observed in normal human tissues, it is a highly specific target for cancer therapy, which is particularly critical for gliomas, where nonspecific targeting effects can cause devastating inflammation of the brain.

In the phase 2 study, 23 patients with GBM received three vaccines at two-week intervals and then proceeded to monthly vaccination after undergoing conformal radiation and concurrent temozolomide therapy. The vaccinations were well-tolerated, and the toxicity was minimal. The following were the results of this trial:

•Median time to tumor progression in the vaccine-treated patients was 12.1 months, which compared favorably with a historical unvaccinated cohort with a median time to tumor progression of 7.1 months.
•Results compared favorably with the current standard of care of GBM treatment, consisting of temozolomide and radiation, with a median time to progression of 6.9 months.

"This trial demonstrated a 70% increase in delaying the time to disease progression, as well as a marked increase in patient survival compared to historical controls," remarked Dr. Heimberger. "In fact, median survival has not yet been reached in the vaccine-treated group of patients." Among recurrent tumors, 100% no longer expressed the EGFRvIII, suggesting that the immune system may have eliminated EGFRvIII-expressing cells; however, this also indicates one potential mechanism of treatment failure. "More extensive research is needed to explore the ramifications of that finding," added Dr. Heimberger.

"This type of immunotherapy approach will be easy for physicians to administer since it can be provided 'off the shelf' and does not involve labor-intensive manipulation of the patient's immune cells," concluded Dr. Heimberger. Preparations are currently underway for a multi-institutional randomized clinical trial.

John H. Sampson, MD, PhD is co-principal investigator for this trial. Co-authors are S. Farzana Hussain, PhD, Dima Suki, PhD, Weiming Shi, MD, Kenneth Aldape, MD, Lamonne Crutcher, RN, Mark Gilbert, MD, Raymond Sawaya, MD, Gary Archer, PhD, Deborah Smith, RN, Henry S. Friedman, MD, David Reardon, MD, Allan Friedman, MD, and Darell Bigner, MD, PhD.


SOURCE: American Association of Neurological Surgeons

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