Patients with advanced follicular non-Hodgkin's lymphoma who received a new combination of chemotherapy and targeted radiation (radioimmunotherapy) lived significantly longer than patients treated with standard chemotherapy alone on previous trials. Five-year follow-up data from the phase II trial was published in the September 1 issue of the Journal of Clinical Oncology.
The long-term follow-up data from the phase II clinical trial (S9911) shows that 5 years after the new treatment, 87% of the patients survived and 67% of the patients survived without their disease progressing. In comparison, using historical data, only 64% were still alive and 44% survived without disease progression after 5 years on the standard chemotherapy treatment.
The new treatment piggy-backs onto the standard treatment by delivering a one-two punch to the cancer cells, explained Oliver Press, MD, who led the study for the Southwest Oncology Group (SWOG). Standard therapy for the disease uses the CHOP regimen (cyclophosphamide, doxorubicin HCl, vincristine [Oncovin], prednisone). Patients in the trial received six 21-day treatment cycles of CHOP. Those who tolerated the treatment without progression were given the new treatment, tositumomab and iodine I-131 tositumomab (Bexxar).
"We feel that the 5-year results of the trial are tremendously encouraging and some of the best ever observed in a SWOG clinical trial for patients with advanced follicular non-Hodgkin's lymphoma," said Dr. Press, who is a member of the Fred Hutchinson Cancer Research Center, professor of medicine at the University of Washington, and chairman of the scientific advisory board of the Lymphoma Research Foundation.
"While patients usually respond initially to CHOP therapy, most patients eventually recur. We feel that this new combination of drugs with antibodies such as tositumomab/iodine I-131 tositumomab show real promise. Not only are patients living longer, they seem to be living relatively symptom-free after the conclusion of their therapy," Dr. Press said. The phase II study was conducted at 34 SWOG institutions with 90 patients who have advanced-stage NHL but had not been previously treated for the disease.
The initial success of the SWOG phase II trial prompted SWOG to open a phase III intergroup trial in 2001 known as S0016. The phase III trial is still open for registration to patients who have never been treated for follicular NHL and whose disease expresses the CD20 antigen. The Cancer and Leukemia Group B (CALGB) and Eastern Cooperative Oncology Group (ECOG) are also participating in this study.
Phase III Study Design
The phase III study compares CHOP plus tositumomab/I-131 tositumomab to CHOP plus a different targeted antibody, rituximab (Rituxan). The investigation was initially designed to compare three types of treatment-CHOP, CHOP plus rituximab, and CHOP plus tositumomab/I-131 tositumomab. However, the CHOP-only arm of the study was closed in 2002, based on results from several completed clinical trials that demonstrated significantly improved response rates and progression-free survival in the CHOP-plus-rituximab arm compared to CHOP alone, making CHOP plus rituximab the new standard therapy.