Vaccine Studies Offer Hope for Brain Cancer Patients
Article date: June 2, 2008
Results from two pioneering studies led by researchers from Duke University Medical Center offer hope to patients with glioblastoma multiforme (GBM), one of the more common and deadliest types of brain tumors.
Both studies involve the use of vaccines in conjunction with chemotherapy to try to boost the body’s immune response against the cancers. Preliminary results were presented over the weekend at the American Society of Clinical Oncology's Annual Meeting in Chicago.
In the first study, the researchers tested a vaccine that targets epithelial growth factor receptor variant III (EGFRvIII), a protein that's found in about half of all GBM tumors. The vaccine was given to 23 patients along with temozolomide (TMZ), the standard chemotherapy treatment for patients with GBM. On average, the combination more than doubled the time it usually takes for these cancers to begin growing again, and seemed to help them live longer as well. Patients treated with standard therapy typically live an average of 14.3 months; the average time for the study participants was 33.1 months.
"We're more than doubling survival time in this group, and we have some patients who are 4, 5, or 6 years out from diagnosis, which is virtually unheard of in these people," said lead researcher John Sampson, MD, PhD, a neurosurgeon at Duke. "The possibility of doubling expected survival—with few if any side effects—would represent a big step and a lot of hope for this group of patients."
The vaccine is thought to work by enhancing the body's immune response to EGFRvIII, prompting the body to kill off and prevent the growth of cells that have the protein -- the GBM tumor cells. The treatment is administered every 2 weeks for the first 3 doses and every month thereafter. Patients have reported minimal side effects, except for swelling at the injection site and fatigue common with chemotherapy treatment regimens.
"While the body is recovering from chemotherapy, immune response is actually stronger as the immune system overcompensates in order to right itself," said Sampson. "It's actually the perfect time to introduce a vaccine."
In order to qualify for the study, patients had to meet several criteria. Their tumors must have been mostly removed through surgery, and they must have already completed standard radiation treatment for GBM. And in order to continue the treatment, they must stay disease-free.
Patients who have had good results with the regimen continue to travel to Duke every month. Cameron Mitchell, of Grand Rapids, Michigan, has been making the trip for the last 4 years.
"You're wiped out for a couple days after the treatment, but it's a small price to pay," said Mitchell. "I'll keep going as long as it keeps working."
Based on the encouraging results from this trial, a larger phase II/III study is now open at more than 20 sites in the US and in Canada.
The second study focused on a vaccine targeting cytomegalovirus (CMV), a type of herpes virus often seen in the blood of people with GBM.
"Previous work has demonstrated the activation of this virus in patients with GBMs, so we took it one step further and tested a vaccine, in a small group of patients, that seems to show some efficacy in stalling the recurrence of these deadly tumors," said Duane Mitchell, MD, PhD, lead researcher of the study at Duke. "We knew there was a connection between this virus and the brain cancer, and we were hoping to take advantage of that connection to treat one by treating the other."
Twenty-one GBM patients were given the vaccine in combination with TMZ after undergoing standard treatment. Mitchell and his colleagues found that the regimen appeared to double the expected disease-free survival time and extend overall survival time from about 14 months with standard treatment to more than 20 months.
Additional studies of this vaccine are also planned.
Citations: "Effect of EGFRvIII-targeted vaccine (CDX-110) on immune response and TTP when given with simultaneous standard and continuous temozolomide in patients with GBM." First author: J. H. Sampson. Abstract No: 2011.
"Efficacy of a phase II vaccine targeting Cytomegalovirus antigens in newly diagnosed GBM." First author: D. Mitchell. Abstract No: 2042.
Reviewed by: Members of the ACS Medical Content Staff
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