The place of third-generation regimens in the treatment of adult aggressive non-Hodgkin's lymphoma

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Abstract
Diffuse large cell lymphoma, the most common form of aggressive non-Hodgkin's lymphoma, has been known to be curable with combination chemotherapy for almost 20 years. Although occasional patients were cured with regimens like COP (cyclophosphamide/vincristine/prednisone) the development of four-drug regimens made cure possible in a significant percentage of patients. Subsequently, newer, so-called third-generation regimens incorporated even more drugs with an apparent increase in the cure rate. However, the identification of important clinical and biologic features in the patient or the tumor that predict for treatment outcome (prognostic factors) has complicated comparison between nonrandomized and nonconcurrent trials. Recently, the Southwest Oncology Group presented data from pilot studies showing that patients treated with ProMACE-CytaBOM (procarbazine/methotrexate/doxorubicin/cyclophosphamide/etoposide-cytarabine/bleomycin/vincristine/ methotrexate), m-BACOD (methotrexate-bleomycin/doxorubicin/cyclophosphamide/vincristine/dexamethasone), and MACOD-B (methotrexate/doxorubicin/cyclophosphamide/vincristine/dexamethasone-bleomycin) did not seem to do better than patients treated in the past with CHOP (cyclophosphamide/doxorubicin/vincristine/ prednisone). Also, the Eastern Cooperative Oncology Group has presented a study in which patients treated with a six-drug regimen did no better than those treated with a CHOP-like regimen. Some have interpreted these reports to mean that all patients with diffuse large cell lymphoma should receive CHOP, since they feel it to be safer. I believe this is not a good interpretation of the available data for the following reasons: (1) when administered at maximum tolerated doses, CHOP has the same approximate 5% treatment-related mortality seen with all regimens; (2) when CHOP is given at reduced (ie, safer) doses, it is not as effective; and (3) it is not yet clear that all patients with diffuse large cell lymphoma are the same in their response to treatment. That is, some patients might have a higher chance for cure with one or another regimen. My interpretation of the available data is that at present each oncologist should choose the regimen in which he or she has the most confidence and become expert in its use. By becoming an expert in the use of a particular regimen it is possible to minimize treatment-related mortality and give patients the maximum chance for a good outcome. It is also important that clinical trials continue to identify the optimal treatment for each subgroup of patients with diffuse large cell lymphoma.