The targeted drug, iodine-131 tositumomab (Bexxar), which is easier to take and less toxic than standard chemotherapy, could one day be the treatment of choice for people with late-stage follicular lymphoma. That's the view of the researchers who originally developed Bexxar, based on results from a phase II clinical trial reported in the February 3 New England Journal of Medicine.

Bexxar is currently approved to treat follicular lymphoma after chemotherapy fails, but researchers at the University of Michigan believe it has potential as a first-line treatment.

The phase II trial included 76 patients with advanced-stage follicular lymphoma. Nearly all of the patients (95 percent) responded to treatment, and three out of four were free of the disease after a single course of treatment, the study found. Five years later, most of the patients were in remission, the researchers added.

"We're pleased that almost all the patients responded, but even more important is the number of patients who achieved complete remission," said Dr. Mark Kaminski, who led the trial.

"This regimen compares favorably to even the most aggressive treatments, especially when you consider that it only takes 1 week to administer compared to several months for chemotherapy," Dr. Kaminski explained. However, he added that the only way to know how effective Bexxar is compared with standard chemotherapies is to conduct a randomized trial.

Such a comparative trial is warranted based on the new results, concurred Dr. Joseph Conners of the British Columbia Cancer Agency in an accompanying commentary. He noted, however, that the patient group in the study was overall slightly younger and perhaps healthier than patients in other trials. In addition, Bexxar was not tested on people with more than 25 percent of their bone marrow affected.

Dr. Wyndham Wilson of the Lymphoma Section of NCI's Experimental Transplantation and Immunology Branch cautioned, "These results are promising, but it's not at all clear that they're better than standard treatments." He also hoped the phase II study will "generate a random trial comparing treatments."

New treatments are needed. Current therapies can temporarily control follicular lymphoma, but there is no cure and most patients die of the disease or complications from treatment.

Bexxar was developed 15 years ago by Dr. Kaminski and Dr. Richard Wahl at the University of Michigan. They launched the current trial in 1996 based on preliminary evidence that treating relapsed patients sooner rather than later yielded better responses.

"We knew it worked well late in the disease and wanted to know what would happen if used earlier," said Dr. Wahl, now at the Johns Hopkins School of Medicine. "The idea was to take your best shot with the best agent early on. If something is working better than chemotherapy, why wait?"

Bexxar is a type of radioimmunotherapy that shrinks tumors through both radiation and an immune response. The drug consists of a radioactive atom (I-131) attached to an antibody on the surface of cells. In the bloodstream, the radioisotope is guided to lymphoma cells by the antibody, where it binds to protein, selectively delivering its radioactivity.

The therapy is tailored to the patient on two levels, explained Dr. Wahl. The drug targets only certain cells in the body, and the dose is determined for each patient individually. Doctors inject the drug and use imaging tools to monitor the body's response. The therapeutic dose is delivered a few days later.

By Edward R. Winstead