GM-CSF is in the same class of drugs as interferon and interleukin, which, as cytokines, are all substances that are produced naturally by the immune cells in small amounts.
One such agent, GM-CSF, is a cytokine, a member of the same family as the only treatment approved by the U.S. Food and Drug Administration (FDA) for adjuvant therapy of melanoma - interferon.
But Lynn Spitler, M.D., explains interferon has some problems that agents such as GM-CSF may not have.
Special interest An internist and immunologist at the Northern California Melanoma Center in San Francisco, Dr. Spitler has been researching melanoma for 30 years with a special interest in immunopotentiator drugs to boost the immune response, particularly in the adjuvant setting - trying to prolong the survival in patients who have already been diagnosed and had surgical treatment for melanoma.
Currently, researchers are looking at ways of modulating the immune response in melanoma patients, according to Dr. Spitler: vaccines to induce a specific immune response and cytokines to activate microphages.
"The problem with vaccines," Dr. Spitler says, "is that potential efficacy for many of them is limited to patients who have a particular histocompatibility type - that is, they have potential efficacy only in patients who are HLA A2 positive - a type present in only about half of the population."
Activating macrophages For the past 10 years, Dr. Spitler has been studying means of activating macrophages so that they will kill tumor cells and leave normal cells alone. She is working with an agent called GM-CSF, the drug Leukine (Berlex).
In the original studies published in The Journal of Clinical Oncology in 2000, the two-year survival rate of patients in the control group treated with surgery alone was 15 percent with a median survival time of about 12 months. For those treated with surgery and GM-CSF, the two-year survival rate increased to 64 percent with a median survival time of over 36 months."
A randomized phase 3 study is currently under way. It is a six-armed program with 600 patients, more than 400 of whom have been accrued.
A consortium led by the Eastern Cooperative Oncology Group is conducting the randomized study.
Patients who are HLA A2 positive are randomized to placebo, GM-CSF, GM-CSF plus vaccine or vaccine alone, HLA A2 negative patients are randomized to placebo or GM-CSF with 100 patients per arm.
GM-CSF is in the same class of drugs as interferon and interleukin, which, as cytokines, are all substances that are produced naturally by the immune cells in small amounts. Although they are all cytokines, the agents all have different mechanisms of action. These versions of the drug are being produced in the test tube and administered in doses higher than those produced in the body.
"GM-CSF offers the potential for improvement," Dr. Spitler says. "Vaccines offer potential for improvement, and those tests are both in phase 3 studies now. We believe they are less toxic than interferon and if they are shown to be effective - that would represent a definite advance in the adjuvant treatment of melanoma."
Different goal Dr. Spitler says GM-CSF is also being studied for use in conjunction with vaccines but with a different goal.
"It's being used as an agent to boost the response to the vaccine. The dose and the route of administration are different from those used in our studies.
"The term 'vaccine' is not being used in the traditional sense of preventing disease; rather, these vaccines are used to treat patients who already have the disease. The use of the GM-CSF can boost the immune response generated by the vaccine."