What is the role of third generation regimens for initial therapy of non-Hodgkin's lymphomas?

The advances in therapy for aggressive non-Hodgkin's lymphoma have improved the long-term outlook for patients with this disease. However, many questions still remain such as: which combination chemotherapy protocol is the best? Is it necessary to use a third generation regimen, or is CHOP (cyclophosphamide/doxorubicin/vincristine/prednisone) adequate? And finally is the extent of dose intensity that can be achieved with conventional therapy adequate in poor prognosis patients? Although several smaller comparative trials have been done, the four arm trial currently being performed by the South West Oncology Group (SWOG) will represent the largest trial designed to address this issue. One best protocol has not yet been identified as being superior to others for the therapy of patients with aggressive non-Hodgkin's lymphomas. However, certain subsets of patients may benefit from specific protocols. This information can hopefully be gleaned from subset analysis of the SWOG study in the future. At the present time, since one best therapy cannot be identified, physicians should chose a regimen that they are confident in and familiar with it's use. By utilizing a particular regimen, one can minimize the treatment-related mortality and optimize the patient's change for a good outcome. Subset analysis to identify particular groups that may benefit from higher dose intensity will be an important feature for future analysis.