Interpretation of clinical trials in diffuse large-cell lymphoma

Diffuse large-cell lymphoma is one of the neoplasms curable with chemotherapy in an appreciable percentage of patients. However, all patients are not cured and the best combination of agents is not certain. This reflects the lack of completed comparative trials using the regimens that appear most effective. Despite this uncertainty, several principles for the therapy of diffuse large-cell lymphoma can be identified that allow an analysis of the results reported in the literature. These principles include the following: (1) for a regimen to be curative in a substantial number of patients it must achieve a high rate of complete remissions; (2) cure must be accomplished with frontline therapy; (3) drugs must be delivered at curative doses; (4) rapidity of achieving a complete response might be related to chance for cure; (5) prolonged treatment for diffuse large-cell lymphoma is unnecessary; and (6) aggressive therapy is toxic. In analyzing the results with any regimen it is important to have long follow-up since late relapses do occur and initial very positive results tend to decay with greater numbers of patients treated. Applying these principles to the reported chemotherapy studies in patients with diffuse large-cell lymphoma suggest that no one of the new regimens is clearly superior to the others. Also, it is not clear that cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) delivered at full doses to comparable patients is inferior to the newer regimens. The results of ongoing studies comparing these regimens might help resolve these questions.