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Targeted Radiation Therapy Halts Low-Grade Lymphomas

Targeted Radiation Therapy Halts Low-Grade Lymphomas

Radiation therapy targeted at the cellular level can halt the advance of lymphoma while avoiding the major drawbacks of chemotherapy, according to a Stanford University study in the March 1996 issue of Clinical Cancer Research.

The Stanford team used radioimmunotherapy (RIT) with yttrium-90 to treat 18 patients whose low- or medium-grade non-Hodgkin's lymphoma had relapsed after chemotherapy. The patients were not candidates for conventional bone marrow transplants because of the extent of their disease.

The researchers observed significant tumor regression in 13 patients and complete disappearance of the tumors in 6 of the 13. The primary side effect of the treatment was temporarily decreased blood counts, but other side effects of chemotherapy, such as hair loss, weight loss, and nausea, were not observed. Freedom from disease progression lasted for periods ranging from 3 months to more than 29 months.

"Our patients appreciated the mildness of this treatment compared with chemotherapy," said Dr. Susan Knox, an assistant professor of radiation oncology at Stanford and lead author of the paper. "Not only did it work better for most of the patients than their prior chemotherapy, but they felt well for the most part."

"Chemotherapy often can make people feel quite sick," Knox said. "Our patients didn't feel sick. They continued to work, ride horses, play golf and do their normal activities."

Chemotherapy performed on an outpatient basis is frequently the preferred treatment for patients with lymphoma. Chemotherapy can eventually lose its effectiveness in low-grade lymphomas, however, which are more indolent than higher grades of lymphoma but often incurable, Knox said.

Radiation does kill the cancerous cells and can be targeted at them using RIT. This form of radiation therapy delivers radiation directly to the cancer using monoclonal antibodies with attached radioisotopes. The antibodies recognize and bind to targets on cancer cells. When they are injected into a patient's system, the antibodies help concentrate the therapeutic radiation in the cancerous area.

Currently, RIT with yttrium-90 is being evaluated as a treatment alternative in cases where chemotherapy has failed. More studies will be necessary, Knox said, to learn how best to use this new therapy.

Knox is hopeful that RIT with yttrium-90-labeled antibodies will eventually be an outpatient treatment. Chemotherapy is administered on either an outpatient or inpatient basis, depending on the particular drugs used, she said.

The Stanford study was a phase I/II study to evaluate safety as well as effectiveness of RIT with yttrium-90, Knox said. A multicenter phase II study is already in the works; it will provide a larger sample for a true measure of treatment effectiveness. Eventually, in a phase III study, the targeted radiation therapy will be compared with chemotherapy.

"That really is the definitive test," Knox said. "And that will not happen for a while."

Coinvestigators on the Stanford team headed by Knox included Dr. Ronald Levy, professor of medicine and chief of the division of oncology; Dr. Michael Goris, professor of radiology and nuclear medicine; and Dr. Thomas Davis, medical oncology fellow.

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