Interferon Superior to a GMK Vaccine in Preventing Melanoma Relapse
High-dose interferon proved superior to a GMK ganglioside vaccine, a potentially promising cancer therapy, in protecting high-risk patients against a recurrence of their melanoma, according to research from a multicenter clinical trial published in the May 1, 2001, Journal of Clinical Oncology (see the journal abstract).
GMK contains an antigen known as GM2, which has been shown to stimulate the immune system to produce antibodies against a molecule found commonly on melanoma cells. But John Kirkwood, M.D., of the University of Pittsburgh Medical Center and several colleagues reported that both relapse-free survival and overall survival were significantly better for patients receiving high-dose interferon compared to the GMK vaccine. The trial was stopped early when this difference became apparent.
"This study confirms the value of high-dose interferon in improving both disease-free and overall survival," said Scott Saxman, M.D., of the NCI's Cancer Therapy Evaluation Program, "and doctors and patients can be more confident of its potential benefit to patients whose melanoma has been removed but who are at high risk for recurrence."
Saxman also pointed out that this was one of the first major studies that has looked at a vaccine as adjuvant (additional) treatment for high-risk melanoma. He cautioned against judging all investigational melanoma vaccines by these results.
"There are important differences among these vaccines and how they interact with the immune system," said Dr. Saxman, "and the results with this particular vaccine don't mean that other approaches won't work. This is still a young field in which rigorous quality research is being done, and we still have considerably more to do."
In 1995, the U.S. Food and Drug Administration approved high-dose interferon alfa-2b therapy as the standard adjuvant treatment after surgery for melanoma patients considered to be at high risk for recurrence, either because of the thickness of their lesion(s) or because they had lymph node involvement. While interferon has been shown to be a potent regulator of the immune system that can help prevent relapse and improve survival in these patients, it does have significant side effects, including flu-like symptoms (muscle pains, headache, fever and chills); reduction in white blood cell count; changes in liver function; and depression.
Therefore, researchers have been investigating alternative treatments such as vaccine therapy, which introduces certain melanoma-associated antigens (substances that prompt a response from the immune system) into the body. The hope is that they might also protect against relapse, but with fewer side effects.
The trial led by the Eastern Cooperative Oncology Group (ECOG) involved 774 melanoma patients who had deep primary lesions (greater than four millimeters) or cancer that had spread to one or more regional lymph nodes. After complete surgical removal of the cancer, patients were randomly assigned to two groups: one group received high-dose interferon alfa-2b five days per week for a month and then three times per week for 48 weeks, while the other was to receive the GMK vaccine once a week for one month and then at three-month intervals for two years.
The trial was stopped early at 16 months median follow-up because high-dose interferon was producing much better results than the vaccine. While 39 percent of the vaccine-treated patients had relapsed, only 25 percent of the interferon-treated patients had. Based on the data, researchers estimated two-year relapse-free survival at 62 percent in the interferon group versus 49 percent in the vaccine group. Their analysis also suggested a 52 percent increase in the risk of death for patients treated with the GMK vaccine versus interferon. Patients whose cancer had not spread to their lymph nodes seemed to have the greatest reduction in the risk of relapse and death.
This is the third randomized adjuvant melanoma trial conducted by the ECOG that has indicated that high-dose interferon improves relapse-free survival in melanoma patients at high risk for recurrence. Another ECOG trial now under way is evaluating the effectiveness of a different type of vaccine therapy (peptide vaccine) in patients whose disease has been surgically removed but have a high likelihood of recurrence.
Currently a number of investigators are evaluating a range of vaccine therapy approaches in melanoma patients. Other trials are comparing the effectiveness of interferon alfa with other adjuvant treatments for high-risk melanoma, such as chemotherapy and other forms of biologic therapy.
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