Biologic therapy (immunotherapy) for kidney cancer

The goal of biologic therapy is to boost the body's immune system to fight off or destroy cancer cells more effectively. The main immunotherapy drugs used in kidney cancer are cytokines (proteins that activate the immune system). In the past, the cytokines used most often were interleukin-2 (IL-2) and interferon-alpha. Both cytokines cause these cancers to shrink to less than half their original size in about 10% to 20% of patients.

At one point, IL-2 was the most common first-line therapy for advanced kidney cancer, and it may still be helpful for some people. But because it can be hard to give and can cause serious side effects, many doctors now only use it for cancers that aren't responding to targeted therapies.

Patients who respond to IL-2 tend to have lasting responses. IL-2 is the only therapy that appears to result in long-lasting responses, although only a small percentage of patients respond. A cancer has certain characteristics that may help predict if IL-2 will be helpful, and more studies are being done to see which characteristics are most helpful.

Interferon has less serious side effects than IL-2, and may be used by itself or used at a lower dose combined with the targeted drug bevacizumab (Avastin). Common side effects of interferon include flu-like symptoms (fever, chills, muscle aches), fatigue, and nausea.

Combining low doses of both cytokines was once thought to be as effective as high-dose IL-2, with fewer and less severe side effects, but more recent studies have not supported this idea. Most doctors think that high-dose IL-2 has a better chance of shrinking the cancer. High dose IL-2 is only given in certain centers, because it can be very toxic and special care is needed to recognize and treat side effects.

The possible side effects of high-dose IL-2, include:

• Extreme fatigue
• Low blood pressure
• Fluid buildup in the lungs
• Trouble breathing
• Kidney damage
• Heart attacks
• Intestinal bleeding
• Diarrhea or abdominal pain
• High fever and chills
• Rapid heart beat
• Mental changes

These side effects are often severe and, rarely, can be fatal. For this reason, cytokine therapy is not used in people who are in poor overall health to begin with. Only doctors experienced in the use of these cytokines should give this treatment.

Cytokines can also be used as part of some experimental immunotherapy techniques. One approach took special immune system cells called tumor-infiltrating lymphocytes (TILs) that can be found within kidney tumors. These cells were taken from the tumor after surgery. These immune cells were then exposed to cytokines in the lab and then given back to the patient. The hope was that they would attack the cancer cells with fewer side effects than just giving cytokines, but the outcomes were disappointing.

Newer forms of immunotherapy are described in the section, “What's new in kidney cancer research and treatment?”