Immunity Booster May Slow Metastatic Melanoma

CINCINNATI—Cases of metastatic melanoma have increased by 690 percent in the past 50 years, yet few life-extending treatments are available for people diagnosed with the disease.

In an effort to slow cancer growth and improve patient survival, a multi-center clinical trial, led locally at the University of Cincinnati (UC) by Leslie Oleksowicz, MD, will test an experimental new drug that boosts the body’s natural defense system.

Disease-fighting cells in the body—known as cytotoxic T-cells—protect the body from invasion by foreign molecules such as bacteria and viruses or from abnormal cancer cells. Researchers believe that early abnormal cancer cells can sometimes escape the body’s natural defense system by activating a pathway which “turns off” the body’s own immune response against such tumor cells.

But scientists believe they can stop this phenomenon by “revving up” the immune system.

The new drug, ipilimumab (i-pi-LIM′-oo-mab), is a monoclonal antibody that works by blocking the molecule CTLA-4, which is responsible for shutting down the immune system so that the body can fight off foreign cancer cells.

“Ipilimumab blocks cellular interactions that prevent the immune system from eradicating cancerous cells that are growing in the body,” says Oleksowicz, UC associate professor of clinical medicine and a medical oncologist with the UC Barrett Cancer Center at University Hospital. “The drug essentially inhibits the inhibition, which we believe will slow disease progression.”

The current chemotherapy treatment approved by the Food and Drug Administration for metastatic melanoma—dacarbazine (duh-KAR’-buh-zeen)—is effective in only 5 to 20 percent of patients.

For this phase-3 trial, researchers are looking for about 200 patients from across the United States who have been diagnosed with inoperable stage-3 or stage-4 melanoma.

Melanoma is the most aggressive form of skin cancer. It occurs when cancerous cells form in the skin’s melanocytes, the cells that produce the pigmentation that gives humans natural body color. Excessive exposure to the sun and artificial light sources—such as tanning beds—is associated with an increased risk for the disease.

Participants will be randomized into one of two treatment arms to receive a six-month treatment regimen of either ipilimumab and dacarbazine or dacarbazine and a placebo.

All medications will be given intravenously every three weeks. Each treatment will last 1 to 1½ hours and can be administered at most UC-affiliated clinics. Response to the drugs will be monitored using regular blood tests and physical examinations that may include bone scans and various imaging studies.

According to the American Cancer Society, nearly 60,000 people—including about 2,300 from Ohio—will be diagnosed with melanoma in 2007. Because there are few treatment options, the average life expectancy for someone with metastatic melanoma is three months to a year.

For more information on study eligibility, call Ruth Steele at (513) 584-2951.

Oleksowicz has no financial interest in Bristol-Myers Squibb, sponsor of the study.