Every year, about 15,000 Americans are affected by follicular lymphoma, a slow-growing but determined cancer with a median survival rate of seven to 10 years after diagnosis. Traditional medicines have been powerless to boost survival outcomes, but a recent study is opening a new window of hope.
The study, led by Dr. Oliver Press of the Center's Clinical Research Division and colleagues from the Southwest Oncology Group (SWOG), indicates that a new treatment clobbers cancer cells with a one-two punch of traditional chemotherapy followed by treatment of a radiation-carrying antibody. The most popular treatment for lymphoma uses four chemotherapy drugs known collectively as CHOP: cyclophosphamide, doxorubicin, vincristine and prednisone. When combined with the relative newcomer Bexxar, the trade name for a radiation-carrying antibody, the mix is powerful.
Published Sept. 1 in the Journal of Clinical Oncology, the study was the first to combine chemotherapy with targeted radiation and showed that 87 percent of the 90 patients treated with the combination survived five years. The historical five-year survival rate of patients treated only with traditional chemotherapy is 64 percent.
"For the past 30 years, textbooks have said that survival for follicular lymphoma was not impacted by any of our treatments," Press said. "Traditional teaching has implied that available therapies shrink the lymph nodes, reduce symptoms and improve the quality of life, but don't cure patients or prolong survival."
The new regimen consists of six 21-day cycles of CHOP chemotherapy followed four to eight weeks later by Bexxar, the GlaxoSmithKline name for tositumomab/iodine I-131 tositumomab. All patients in the study had previously untreated, advanced-stage follicular lymphoma.
"The study with CHOP followed by Bexxar has had the best results of any study in the history of the Public Health Science Division's SWOG for follicular lymphoma in terms of response rates, remission durations, freedom from disease progression, overall survival and all the other measures that are usually used to determine how effective a treatment is," said Press, who is also an oncology specialist at the Seattle Cancer Care Alliance and professor at the University of Washington.
Press pointed out that the study's 23 percent increase is based on a historical comparison, so to definitively prove that survival did indeed increase, researchers are conducting a randomized study. Nearly 400 people have been treated on the randomized study. "We're very optimistic about the results of the ongoing randomized trial," Press said.
How combination therapy works
"Initial response to traditional CHOP therapy is usually positive, but most patients eventually see a relapse, which is one of the reasons this new therapy is so exciting," Press said. "Patients are living longer, relatively symptom-free, five years after the combination treatment."
Follicular lymphoma is a type of non-Hodgkin's lymphoma, or cancer of the immune system, that affects B-cells, a type of white blood cell involved in the body's immune system. The therapy works because the radiation-carrying antibody hones in on a specific protein on the surface of normal and cancerous B-cells and binds to it. The thousands of delivered antibodies swarm to the location where B-cells are concentrated, effectively producing a high dose of radiation in a targeted area of the body.
Phase II study
Because Bexxar only targets B-cells, it is not a likely therapy for other forms of cancer, but researchers are hopeful that other types of lymphomas could take a hit from the combination. "Many, many types of lymphoma are being investigated," Press said, noting that other studies are under way to determine the effectiveness of the new treatment in other lymphomas.
The Food and Drug Administration approved Bexxar for treating patients with relapsed or refractory follicular lymphoma, but the drug has not been approved as a front-line therapy.
SWOG researchers opened the Phase II study in the spring of 1999 to determine whether the combination treatment was safe and effective. They found that most of the negative side effects were related to traditional chemotherapy, not the radiation-carrying antibody.
"Since this study was the first to combine CHOP with Bexxar, we didn't know how patients would tolerate those two given in rapid succession, so we were very pleasantly surprised. There were no treatment-related deaths in the study and very few serious toxicities," Press said. "We're very excited about this."
Funding for this study was provided by National Institutes of Health grants to SWOG.