Vaccine first to show improved survival rates for metastatic melanoma

(Press-News.org) (CHICAGO) – For patients with advanced melanoma, which is the most lethal type of skin cancer, the results of a large clinical trial show that a vaccine combined with the immune-boosting drug Interleukin-2 can improve response rate and progression-free survival.

The findings of the study were published in the June 2 issue of New England Journal of Medicine. This marks the first vaccine study in the disease and one of the first in all cancers to show clinical benefit in a randomized Phase III clinical trial.

"This is the first time that a vaccine has shown benefit in the treatment of patients with metastatic melanoma. The trial is an early example of success with a cancer vaccine," said Dr. Howard Kaufman, director for the Rush University Cancer Center and study co-investigator.

"If we can use the body's own defense system to attack tumor cells, we provide a mechanism for ridding the body of cancer without destroying healthy tissue," said Kaufman, who is also an associate dean of Rush Medical College and a professor in the departments of general surgery, internal medicine and immunology and microbiology at Rush University.

Therapeutic cancer vaccines, unlike typical vaccines that prevent infections, are meant to jump-start the immune system to help it battle existing tumors.

Rush was one of 21 centers in the U.S. participating in the trial. Researchers randomly assigned 185 patients with metastatic melanoma to either a combination of the peptide vaccine, which is a small portion of protein that is present on the surface of the melanoma cancer cells, and Interleukin-2, a drug that activates the immune system, or a high dose of Interleukin-2 alone.

The peptide vaccine, known as gp100:209-217 (200M), works by stimulating the patient's T-cells, which is known for controlling immune responses. The injection primes the immune system to recognize the protein and activates the body's cytotoxic T-cells to recognize the antigens on the surface of the cancerous tumor. The T-cells then secrete enzymes to seek out and destroy the tumor cell's membrane.

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.

Ninety-four patients in the Interleukin-2 arm of the study were enrolled and 93 were treated and evaluated for response. In the Interleukin-2 and peptide vaccine combination arm of the study, 91 were enrolled, 86 were treated and 85 were evaluated for response.

About 16 percent of study participants given the vaccine and Interleukin-2 combination saw tumors shrink by 50 percent or more, compared to 6 percent given Interleukin-2 alone.

Those in the vaccine and drug combination group also had slightly longer progression-free survival rates of 2.2 months compared to 1.6 months, which means those participants had more time in which the tumor did not grow.

Patients given the combination also lived an average of nearly seven months longer than those only give Interleukin-2 -- 17.8 months longer compared to 11.1 months.

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.

According to the American Cancer Society, melanoma has one of the fastest growing incident rates of all cancers. The five-year survival rate for melanoma patients is less than 10 percent.

Interleukin-2 is already FDA-approved to treat metastatic melanoma and kidney cancer.

The next step is to improve the vaccine's efficacy. Researchers hope to improve upon the study's findings by combining the vaccine with other immune-stimulatory agents such as adjuvants, other cytokines and antibodies that further activate the immune cells.

"This is one of the first positive, randomized vaccine trials in cancer and the findings represent a significant step forward for treatment of advanced melanoma," said Kaufman.

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 study was partially funded by the National Cancer Institute.

Rush is a not-for-profit academic medical center comprising Rush University Medical Center, Rush University, Rush Oak Park Hospital and Rush Health.

Rush is currently constructing a 14-floor, 806,000-square-foot hospital building near the corner of Ashland Avenue and the Eisenhower Expressway. The new hospital, scheduled to open in 2012, is the centerpiece of a ten-year campus redevelopment plan called the Rush Transformation, which also includes completion of a new orthopedics building, a new parking garage and central power plant, renovations of selected existing buildings and demolition of obsolete buildings. The new hospital is designed and built to conserve energy and water, reduce waste and use sustainable building materials. Rush is seeking Leadership in Energy and Environmental Design (LEED) gold certification from the U.S. Green Building Council. It will be the first full-service, "green" hospital in Chicago.

Rush's mission is to provide the best possible care for its patients. Educating tomorrow's health care professional, researching new and more advanced treatment options, transforming its facilities and investing in new technologies—all are undertaken with the drive to improve patient care now, and for the future.