Photo by Todd McNaught
A new therapy for an incurable form of lymphoma induced remission in 98 percent of patients, and greater than 80 percent of patients remain disease-free more than two years after treatment, according to a the results of a preliminary clinical trial led by scientists in the Clinical Research Division.
The therapy, which consists of six cycles of chemotherapy followed by treatment with a radioactively-tagged antibody to destroy cancerous cells, could offer new hope to the 15,000 Americans diagnosed with follicular lymphoma each year.
The Southwest Oncology Group (SWOG), a clinical-trials organization sponsored by the National Cancer Institute, conducted the trial. The center's Public Health Sciences Division and Cancer Research and Biostatistics, a non-profit Seattle company, jointly house SWOG's statistical center.
Dr. Oliver Press, principal investigator of the trial, called the results of the preliminary study-known as a phase 2 trial-very promising.
"Patients undergoing this treatment fared better than we've seen with other therapies that have been tested in earlier SWOG clinical trials," said Press, who holds the Dr. Penny E. Petersen Memorial Chair for Lymphoma Research endowed by James and Sherry Raisbeck. "But more definitive answers will emerge after we complete a larger study to compare this therapy to another that has shown good results in small-scale trials."
Trial results are in the Sept. 1 issue of Blood. Co-authors include Drs. Joseph Unger and Michael LeBlanc of the SWOG statistical center; Dr. David Maloney of the Clinical Research Division; Dr. Saul Rivkin, director of the Puget Sound Oncology Consortium; and colleagues at Oregon Health and Science University, the University of Arizona, Loyola University and the University of Rochester Medical Center.
A puzzling disease
Lymphomas are cancers of the lymphatic system, a network of nodes and vessels that play an important role in the immune system. Follicular lymphoma, the second most common form of non-Hodgkin's lymphoma, is a slow-growing disease with few early symptoms that affects a type of white blood cells known as B lymphocytes. Most patients are at an advanced and incurable stage when diagnosed, Press said.
"This is a puzzling disease," he said. "It's not known to be curable with conventional chemotherapy, and patients do not feel very sick.
"There are a lot of available treatments-including stem-cell transplantation-but it's not clear whether any of them prolong survival. It makes the initial conversation with a patient a long and difficult one."
Treatments such as chemotherapy induce remission, although the cancer eventually recurs. Patients typically live about 10 years after diagnosis, with death occurring primarily due to infections.
To test whether survival rates could be improved by combining two existing therapies, Press and colleagues conducted a clinical trial that involved 90 patients with follicular lymphoma between the ages of 23 and 84 who were treated at 27 SWOG-affiliated institutions around the country.
Patients first received six cycles of a combination of drugs known as CHOP (consisting of cyclophosphamide, doxorubicin, vincristine and prednisone), the most common type of chemotherapy for lymphoma.
Next, patients received an antibody (tositumo-mab) that reacts against CD20, a protein found on the surface of B lymphocytes. Antibodies are immune-system proteins that tightly bind to other proteins in a highly specific fashion, ultimately targeting them for destruction by the immune system. To increase the effectiveness of the antibody, the researchers used a modified form tagged with radioactive iodine. Investigators at the University of Washington Department of Nuclear Medicine in conjunction with researchers at Fred Hutchinson were among the first to test this radiolabeled antibody, now known as Bexxar. The antibody destroys both normal and cancerous B cells, although the normal B cells regenerate several weeks after treatment.
Large-scale comparison trial
Produced by the Seattle-based Corixa Corporation, the U.S. Food and Drug Administration approved Bexxar as an effective new drug in June. Former UW and center researchers Drs. Mac Cheever and Patricia Stewart are key members of the Bexxar development team at Corixa.
Eighty-one of the 90 patients achieved remission after treatment. After a two-year follow-up period, the overall survival rate was 97 percent and 81 percent remained free of disease.
Press currently leads a large-scale SWOG clinical trial involving 500 patients nationwide to compare whether CHOP plus the radioactively-tagged antibody is superior to other treatments for follicular lymphoma.