Cyclophosphamide, doxorubicin, vincristine, and prednisone versus intensive chemotherapy in non-Hodgkin’s lymphoma

 Therapy for aggressive non-Hodgkin’s lymphomas has undergone significant evolution in the past 25 years. First-generation combination chemotherapy studies produced complete response (CR) rates of 45 – 53% together with 30 – 37% rates of long-term survival. New treatment programs aimed at increasing CR rates were then developed on the assumption that the additional patients who achieved a CR would become long-term disease-free survivors. Initial reports of single-institution pilot studies with third-generation regimens suggested CR and survival rates of 68 – 86% and 58 – 69%, respectively; however, after longer follow-up periods, survival rates decreased. Furthermore, confirmatory national phase II trials using these newer regimens produced CR rates of only 49 – 65% and survival rates of 50 – 61%. Thus, ultimate conclusions concerning the efficacy of these new regimens awaited the results of prospective randomized trials. The Southwest Oncology Group (SWOG) conducted a randomized trial comparing standard therapy, CHOP, to the third-generation chemotherapy regimens m-BACOD, ProMACE-CytaBOM, and MACOP-B. After 6 years, no difference in the response rate, progression-free survival, or overall survival has been found between CHOP and the third-generation regimens. For example, the 6-year estimates of progression-free survival are CHOP 33%, m-BACOD 36%, ProMACE-CytaBOM 34%, and MACOP-B 32% (P = 0.41). The 6-year overall survival estimates are CHOP 42%, m-BACOD 40%, ProMACE-CytaBOM 46%, and MACOP-B 41% (P = 0.89). Furthermore, we have not identified any subset of patients who survive longer on treatment with the third-generation regimens, and the cost and toxicity of the new regimens are higher. On the basis that <50% of these patients are cured, the best approach for any patient is an experimental one designed to improve our ability to cure the disease. Examples of this include (l) increasing the dose intensity of drugs used in standard regimens and (2) autologous bone marrow transplantation and/or peripheral stem-cell support as rescue from marrow-ablative chemotherapy. If a patient is not eligible or does not wish to participate in a clinical trial, CHOP, as inadequate as it is, remains the gold standard.