Wednesday, June 1, 2011 (HealthDay
For patients with advanced melanoma, the
most dangerous type of skin cancer, a vaccine combined with an
immune-boosting drug is showing promise in a large clinical trial.
Therapeutic cancer vaccines, unlike
typical vaccines that prevent infections, are meant to jump-start the immune
system to help it battle existing tumors.
In this Phase 3 clinical trial, conducted
at 21 care centers, researchers randomly assigned 185 patients with
metastatic melanoma, meaning the cancer had spread, to either the vaccine
followed by interleukin-2, a drug that activates the immune system, or
Those given the vaccine-drug combo showed
more improvement than those given the drug alone, according to the study,
which was published in the June 2 issue of the New England Journal of
About 16 percent of those given the
vaccine/interleukin-2 combination saw their tumors shrink by 50 percent or
more, compared to 6 percent given interleukin-2 alone.
Those in the vaccine/drug group also had
slightly longer "progression-free" survival -- 2.2 months compared to 1.6
months -- meaning they had more time in which the tumor didn't grow.
Patients given the combo also lived an
average of nearly 7 months longer than those only give interleukin-2 --
nearly 18 months compared to about 11 months. While a "strong trend," those
results were not statistically significant, said lead study author Dr.
Douglas Schwartzentruber, medical director of the Goshen Center for Cancer
Care at Indiana University Health.
"This is the first time that a vaccine
has shown benefit in the treatment of patients with metastatic melanoma, and
it's an early example of success with a cancer vaccine," Schwartzentruber
He and the other researchers reported
that although the treatment-related toxic effects were similar in both
groups, the vaccine "added some toxic effects" in the combination therapy
group, including transient heart problems such as an abnormally rapid heart
beat (tachycardia) and arrhythmias (15 percent vs. 2 percent).
In addition, the researchers reported one
treatment-related death in the interleukin-2-only group and two such deaths
in the combination therapy group.
Therapeutic vaccines are being studied
for several types of cancers, with varying degrees of success, said William
Chambers, director of clinical cancer research and immunology for the
American Cancer Society.
In the melanoma trial, "they had a
response. It wasn't a huge response, but clearly there was a fairly
significant number that had a response," Chambers said. "And with this
disease, there has not been a lot of success in treating these patients. The
prognosis has been poor. They learned some significant lessons in this
In order for this vaccine to work,
patients had to have a particular tissue type, called HLA-A2, which is
present in about half of whites.
Last year, the U.S. Food and Drug
Administration approved a vaccine to treat prostate cancer. Researchers at
University of California, Los Angeles are also working on a vaccine to treat
glioblastoma, the most aggressive type of malignant brain tumor.
The melanoma vaccine is based on a
peptide, or a small portion of a protein, that's present on the surface of
the melanoma cancer cells. Known as the gp100 peptide vaccine, the injection
primes the immune system to recognize the protein, so that it then seeks out
cells that produce the protein and destroys them.
The immune-boosting drug, interleukin-2,
enhances the vaccine's effectiveness by stimulating the production of
lymphocytes, a type of white blood cell that circulates throughout the body.
More circulating lymphocytes means there are more cells available to do the
job the vaccine has "educated" them to do, Schwartzentruber said.
The five-year survival rate for melanoma
patients is less than 10 percent, experts said. Interleukin-2 is already
FDA-approved to treat metastatic melanoma and kidney cancer.
The researchers said their next step is
to improve the vaccine's efficacy. They hope by combining the vaccine with
other agents (called adjuvants) or immune-boosting drugs, they might get a
"We have now a strong proof of principal
that with an immunological treatment we can see benefit, but at this point
the benefits are small," Schwartzentruber said. "What we've decided to do is
to try to develop a more potent vaccine before we do another trial."
The vaccine, if eventually approved by
the FDA, would be relatively inexpensive because it is based on a protein
that's present in most melanoma cancers, whereas other vaccines have had to
be created for each individual patient, the researchers said.
The vaccine was developed at the U.S.
National Cancer Institute, which also funded the study.
Douglas Schwartzentruber, M.D, medical
director, Goshen Center for Cancer Care, Indiana University Health; William
Chambers, Ph.D, director, clinical cancer research and immunology, American
Cancer Society, Atlanta, Ga.; NEJM, June 2, 2011.