Comparing Drug Regimens for Diffuse Large B-cell Lymphoma
Name of the Trial
Phase III Randomized Study of Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (R-CHOP) Versus Etoposide, Prednisone, Vincristine, Cyclophosphamide, Doxorubicin and Rituximab (EPOCH-R) in Patients with Previously Untreated De Novo Diffuse Large B-Cell Non-Hodgkin Lymphoma (CALGB-50303). See the protocol summary.
Dr. Wyndham Wilson, NCI Center for Cancer Research; Dr. Andrew D. Zelenetz, Cancer and Leukemia Group B
Why This Trial Is Important
Diffuse large B-cell lymphoma (DLBCL) is an aggressive form of non-Hodgkin lymphoma. Research by NCI scientists on the genetics of DLBCL has revealed that there may be three distinct subtypes of this disease, each characterized by a different pattern of gene expression.
Standard treatment for DLBCL is R-CHOP, which consists of a chemotherapy drug combination known as CHOP along with the antibody rituximab. Treatment with R-CHOP succeeds in curing more than 50 percent of DLBCL patients; however, many patients still experience progressive or recurrent disease and ultimately die from their cancer.
Another form of combination chemotherapy for aggressive lymphomas, called EPOCH, has been developed by NCI researchers. EPOCH contains the same drugs as CHOP, but it also includes the drug etoposide. Similar to CHOP, EPOCH can be paired with rituximab (EPOCH-R). However, several components of EPOCH-R are given as a continuous infusion over a 4-day period, allowing their doses to be adjusted to achieve optimum concentrations in the blood of each patient. The administration of R-CHOP does not allow for such adjustments.
Some evidence suggests that the benefit of rituximab varies with DLBCL subtype. In addition, other research suggests that EPOCH-R may be effective against subtypes of DLBCL that are resistant to R-CHOP. Consequently, researchers want to know if different therapeutic regimens can increase the cure rates for patients with different DLBCL subtypes.
In this trial, patients with previously untreated DLBCL will be randomly assigned to receive either R-CHOP or EPOCH-R for 6 to 8 cycles. Researchers will monitor the patients for event-free survival (the length of time after the start of treatment until the occurrence of a disease-related event, including progression, relapse, or death), response rate, and overall survival, and they will try to correlate these clinical outcomes with the molecular features of each patient’s cancer, as determined by gene expression profiling.
“There are two important endpoints for this trial,” said Dr. Wilson. “First, can EPOCH-R produce better clinical outcomes than R-CHOP for patients with DLBCL? Second, can we use gene expression profiling to determine prognostic molecular characteristics that will tell us which patients benefit most from these different regimens?”