Melanoma immunology trials surveyed

March 1, 2005

New Orleans — Because metastatic melanoma is a condition that can be treated, but for which an effective cure remains elusive, many practicing dermatologists are encouraged to learn about the various clinical trials, including immunotherapy trials, in which their patients may be eligible to participate.

New Orleans - Because metastatic melanoma is a condition that can be treated, but for which an effective cure remains elusive, many practicing dermatologists are encouraged to learn about the various clinical trials, including immunotherapy trials, in which their patients may be eligible to participate.

"When the primary melanoma is thin, you can get a 95 percent-plus cure rate simply by excising it. But let's say it is already metastatic or that, with surgery, the patient's melanoma clears, but you know that there is a high rate of recurrence, and the melanoma is not amenable to further surgery; you look for other modalities of treatment," says Henry C. Maguire, Jr., M.D., professor of oncology and dermatology, Thomas Jefferson University Hospital in Philadelphia.

"We don't have any very successful chemotherapy treatments for melanoma, and melanoma is a radio-resistant tumor, so that the usual ways of treating advanced cancers often don't work. Some tumors melt away with X-rays, such as lymphomas, but melanoma is on the other side of the spectrum," he explains.

According to Dr. Maguire, attempts to treat cancerous tumors with immunological therapies are more than 100 years old. One of the earliest physicians to clinically observe results in this area was Dr. William Coley, a New York surgeon at New York Hospital who treated cancers with killed streptococci and with other bacteria, with some success. The mechanism of action probably was based on an inflammatory response with the liberation of cytokines that were toxic to the tumor cells.

"Our understanding of immunotherapy is rapidly advancing and should be translated into clinical results in the next few years," Dr. Maguire says.

Approved therapies Two immunological therapies have already been approved for melanoma. The oldest is a method of injecting the tumor with a live but attenuated strain of tubercule baccili (BCG). The method was developed several decades ago. The organism causes inflammation of a sort that is especially toxic to tumor cells, and is considered standard therapy, Dr. Maguire says.

The other immunological therapy for melanoma is with alpha-interferon. In this country, alpha-interferon is available from Schering-Plough and has been out for five or six years, Dr. Maguire says.

"It is very widely used now for patients who've been surgically cured of their disease but have a significant possibility of recurrence. The down side of the treatment is that you have to give the drug in high doses, and it is quite toxic. There is also some argument about how well it works, and whether it simply postpones the return of the tumor," he says.

A large number of therapies are in clinical trials. These include trials with different cytokines, such as Il-2, Il-12 and IL-15, and various tumor antigens. Some trials use as antigen for making a vaccine the patient's own tumor cells, or melanoma cells or extracts that have been derived from another patient - the cells are rendered non-viable before use. A number of different immunological adjuvants are used to increase the immune response.

Disclosure: Dr. Maguire had no financial interests to disclose relevant to this presentation.

For more information: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi/