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New treatment rivals chemotherapy for lymphoma


95 percent of patients respond to radioactive antibody treatment

A new form of treatment for lymphoma that takes a fraction of the time of traditional chemotherapy with fewer side effects caused tumors to shrink in 95 percent of patients, a new study by researchers at the University of Michigan Comprehensive Cancer Center found.

Patients with advanced-stage follicular lymphoma – a cancer generally considered incurable – who had not been previously treated with any other form of therapy received a single course of treatment with the Bexxar therapeutic regimen, a radioactive antibody injected into the bloodstream that targets and kills cancer cells. Of the 76 patients enrolled in the study, 95 percent responded to the treatment and 75 percent had a complete response, meaning no evidence of cancer remained. More than three-quarters of patients with a complete remission were disease-free after five years.

Results of the study appear in the Feb. 3 New England Journal of Medicine.

"The results of this treatment, which essentially takes only one week to complete, rival any kind of treatment that’s been used for follicular lymphoma, including chemotherapy regimens that take months to complete. It’s very well-tolerated by patients and we saw complete remission in the majority of patients lasting for years," says lead study author Mark Kaminski, M.D., director of the Leukemia/Lymphoma Program and the Multidisciplinary Lymphoma Clinic at the U-M Comprehensive Cancer Center.

Kaminski and his colleague Richard Wahl (formerly at U-M and now at Johns Hopkins University) developed the Bexxar regimen, which received approval from the U.S. Food and Drug Administration in June 2003 to treat follicular non-Hodgkin’s lymphoma after other treatments have failed. The newly published research involves Bexxar as a first-line treatment for this disease.

Non-Hodgkin’s lymphoma, the nation’s sixth leading cause of cancer death, is a cancer of the lymph system, which is part of the immune system. Lymphoma spreads easily through the lymph system and the bloodstream and consequently tends to be widespread when it is diagnosed. Traditional treatment often involves intensive chemotherapy, or a combination of chemotherapy and the monoclonal antibody rituximab. These treatments are usually given every three weeks over a span of up to six months and can cause many unpleasant side effects, including nausea, hair loss and infections.

Follicular lymphoma is the second most common type of non-Hodgkin’s lymphoma and is not considered to be curable using these traditional treatments; even after patients initially have a response to treatment, the disease almost always comes back and becomes more difficult to treat.

Bexxar, whose chemical name is tositumomab and iodine I 131 tositumomab, combines an antibody that seeks out cancer cells, and a radioactive form of the element iodine. When injected, it travels like a guided missile through the bloodstream to bind to a protein found on the surface of the cancerous cells. The radiation zaps these malignant cells with minimal exposure to normal tissues.

With the Bexxar therapeutic regimen, a patient receives an injected test dose of radioactive Bexxar to determine how that patient’s body processes the tagged antibody. Nuclear medicine scans are used to assess how quickly Bexxar reaches the tumor and how quickly the radiation disappears from the patient’s body. One to two weeks after that initial dose, the patient then receives a custom-tailored therapeutic dose, and therapy is considered complete. The most common side effect is a temporary lowering of blood counts several weeks after the treatment. There is no hair loss and nausea is rare.

Results from this study are even more promising than results using Bexxar after other therapies have failed. In those studies, 70 percent of patients responded to Bexxar and 20 percent to 30 percent saw a complete remission. Bexxar is marketed in the United States by GlaxoSmithKline.

"Given how much better this treatment worked as first-line therapy in our study, moving this treatment up earlier in the course of a patient’s illness should be strongly considered instead of using it as a last resort or not at all. These results support the notion that there’s a real possibility of putting chemotherapy on the back burner for this disease," says Kaminski, a professor of internal medicine at the U-M Medical School. "New studies can now be designed to begin to test this possibility," he adds.

In addition to Kaminski, U-M study authors are Melissa Tuck, research associate for Hematology/Oncology; Judith Estes, M.S.N., N.P., nurse practitioner in the lymphoma clinic; Charles W. Ross, M.D., associate professor of Pathology; Kenneth Zasadny, Ph.D., Nuclear Medicine; Denise Regan and Paul Kison, nuclear medicine technicians; Susan Fisher, project associate in Radiology. Other authors are Stewart Kroll from Corixa Corp.; Arne Kolstad, M.D., Ph.D., from the Norwegian Radium Hospital, Oslo; and Richard L. Wahl, M.D., from Johns Hopkins University School of Medicine.

Nicole Fawcett | EurekAlert!
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