Radio-Immunotherapy Holds Promise for Patients with Lymphoma

"I'm sorry, Mrs. Wolter, but your cancer is back." Charlotte Wolter had heard this before. The Glencoe, MN, resident had endured seven months of chemotherapy. And now, after participating in a clinical trial she had hoped would put her cancer into remission, she was hearing the words again.

For Wolter and many other patients battling B-cell non-Hodgkin's lymphoma, chemotherapy and radiation often result in tumors shrinking but recurring in the same or other locations. At the same time, there is no cure for the disease. These patients brave difficult treatment regimens, endure a host of side effects, yet still fail to hear those magic words: you're cancer-free.

But now a new drug, known as Zevalin, is giving hope to patients who no longer respond to other treatment options. For patients like Wolter, Zevalin appears to be a wish come true.

Charlotte's Story

Wolter was diagnosed with low-grade, B-cell non-Hodgkin's lymphoma in November 1997 and began chemotherapy almost immediately. When the treatment failed to cure her cancer, she knew what she wanted to do.

"After finding out my cancer had come back, I was devastated," says Wolter.

"I asked my husband, 'Do you know what I want to do, in the bottom of my heart?'"

"Go to Mayo?" asked her husband, Richard.

"Yes."

The Wolters traveled to Rochester and met with Thomas Witzig, M.D., a hematologist. After reviewing her medical history, Dr. Witzig informed Wolter that she qualified to participate in a clinical study on a drug called Rituxan, a precursor to Zevalin. She eagerly signed up for the study, received the treatment, and waited. Six months later, Wolter received the disheartening news that her cancer had relapsed.

Dr. Witzig had one more option in mind for Wolter. Because her cancer had been very resistant to treatment, she qualified for another clinical study. This time, the drug being tested was Zevalin, and again, Wolter pinned her hopes on a treatment physicians were only beginning to fully understand. This time, her hopes were realized. Wolter received Zevalin in June 1999, and her cancer has been in remission ever since.

How it Works

Zevalin is a monoclonal antibody, which is an antibody produced in a laboratory and engineered to identify and affix to specific cells. Radiation then can be attached to that antibody. Patients treated with Zevalin receive an intravenous mixture of the antibody and radiation. This mixture travels through the bloodstream and stops at the lymphoma cells, radiating only the cancerous tissue. This type of treatment is called radioimmunotherapy.

The ability to target specific cells is what makes Zevalin unique and of such great benefit to patients. "Patients with lymphoma are almost always responsive to radiation, but many times we can't radiate the entire body because we will damage normal organs and healthy tissue," says Gregory Wiseman, M.D., a nuclear medicine specialist who administers radioimmunotherapy. "Because lymphoma many times is a generalized cancer, we haven't been able to utilize external radiation as fully as we would like. Zevalin has enabled us to administer radiation in a new and very effective way."

Physicians and patients are excited about Zevalin because it is administered over a short period of time and on an outpatient basis. Unlike chemotherapy, which requires several treatments a week over the course of many months, Zevalin is administered in two doses within a single week. Also unlike chemotherapy, Zevalin has less side effects. "Patients undergoing chemotherapy often experience nausea, vomiting, hair loss and fatigue," says Dr. Witzig. "With Zevalin, the only side effect of consequence is a temporary reduction in blood count. Most patients aren't even aware of this reduction."

From Laboratory to Clinical Practice

Researchers at IDEC Pharmaceuticals Corporation in San Diego began developing what would become Zevalin more than 10 years ago. Initial experiments on mice showed that the antibody could bind to lymphoma cells and deliver radiation to the cells. But before Zevalin or any other drug is made available to patients, it must gain approval from the Food and Drug Administration. This approval process takes years and requires a series of clinical trials proving both the effectiveness and safety of the drug.

Dr. Witzig and Dr. Wiseman had been following the development of Zevalin and applied to participate in the clinical trials. Their application was accepted, and Mayo became one of 10 cancer centers involved in studies that would eventually lead to Zevalin's FDA approval. In the study, Drs. Witzig and Wiseman found that tumors shrunk in 80 percent of patients receiving Zevalin. Thirty percent of patients receiving Zevalin experienced a complete remission of their cancer. Wolter was delighted to be among this 30 percent. And she was equally delighted to participate in the study.

"People have asked me if I had a difficult time deciding to participate in the studies," says Wolter. "It really wasn't a hard choice for me to make. Many years ago, people volunteered to be among the first to try chemotherapy, and without them, a lot of people with cancer wouldn't be here now. I feel that by participating in the studies, I am doing something important not just for myself, but for people who come after me, too."

Incidence on the Rise

While the incidence of most cancers has been declining, that of non-Hodgkin's lymphoma has been on the rise. It is the fifth most common type of cancer diagnosed in the United States, with an estimated 300,000 Americans currently living with the disease.

Physicians aren't sure why they are seeing more patients with non-Hodgkin's lymphoma. Dr. Wiseman says one possible explanation is our increased exposure to chemicals and pesticides. Another possibility is an increase in the number of people susceptible to the disease because their immune systems are compromised due to an organ transplant or HIV infection.

While the incidence of lymphoma is on the rise, so are the options physicians have to choose from when treating the disease. "This is the beginning of an entirely new way to treat cancer," says Dr. Witzig. "I think we will continue to see drugs like Zevalin being developed to treat other types of cancer, including breast and colon cancer. There is a tremendous amount of potential and hope for Zevalin and other radioimmunotherapies." And that's good news for us all.