Study Shows Combination Of Immune Substances To Be Safe

Normally, interferon is used alone to stimulate the immune system to attack certain cancers. This strategy, a form of immunotherapy, is sometimes used to treat melanoma, advanced kidney cancer and other tumors that respond poorly to chemotherapy or radiation therapy. But interferon can have serious side effects that limit its use.

Surprisingly, the two drugs used in sequence caused no serious side effects in patients.

"Interferon can be quite toxic when used alone," says principal investigator William E. Carson, III, associate professor of surgery and associate director for clinical research at the Ohio State University Comprehensive Cancer Center.

"We were initially concerned that the addition of IL-12 might increase that toxicity. Instead, we found that the two drugs can be used together without additional side effects."

The findings are published in the December 1 issue of the Journal of Clinical Oncology. They suggest that IL-12 primes white blood cells such that a lower dose of interferon will stimulate the same level of immune activity as a higher dose of interferon when used alone.

The results come from a phase-I clinical trial, which marks the first time a treatment is tried in human subjects. The trial, conducted by Carson and a team of colleagues, involved 49 patients ages 23 to 84 with different types of advanced cancer, including cancers of the colon, lung, kidney and bladder and melanoma.

On the first day of treatment, patients were given IL-12, initially by injection and then intravenously. That was followed by injections of interferon over the next five days. On average, patients received five such cycles over the course of the study.

The drug combination not only proved to be safe -- which was the purpose of the study -- but the researchers found that it stopped disease progression in five of the patients for at least six months.

"Our findings were encouraging," Carson says. "They indicate that we can safely administer IL-12 in combination with interferon, that it enhances the action of interferon in some patients with advanced cancer, and that it can be an effective way to stimulate the immune system."

Based on the study's results, and the results of earlier animal studies led by the research group, Carson and his colleagues are conducting a multicenter phase II clinical trial of the two drugs in people with melanoma.

Phase-II trials are the first step in determining the effectiveness of new therapy against a specific disease.

"We believe that use of the two drugs together will give us more bang for the buck," says first author Gregory B. Lesinski, a research assistant professor in the Human Cancer Genetics Program.

"We hope that the IL-12 will allow us to use lower doses of interferon in patients, which should result in fewer side effects and potentially a longer use of interferon, giving the immune system more time to fight the tumor."

Funding from the National Cancer Institute and The Valvano Foundation for Cancer Research Award supported this research.