CYCLOPHOSPHAMIDE, DOXORUBICIN, VINCRISTINE, AND PREDNISONE VERSUS INTENSIVE CHEMOTHERAPY IN NON-HODGKINS-LYMPHOMA

Therapy for aggressive non-Hodgkin's lymphomas has undergone significa nt evolution in the past 25 years. First-generation combination chemot herapy studies produced complete response (CR) rates of 45-53% togethe r with 30-37% rates of long-term survival. New treatment programs aime d at increasing CR rates were then developed on the assumption that th e additional patients who achieved a CR would become long-term disease -free survivors. Initial reports of single-institution pilot studies w ith third-generation regimens suggested CR and survival rates of 68-86 % and 58-69%, respectively; however, after longer follow-up periods, s urvival rates decreased. Furthermore, confirmatory national phase II t rials using these newer regimens produced CR rates of only 49-65% and survival rates of 50-61%. Thus, ultimate conclusions concerning the ef ficacy of these new regimens awaited the results of prospective random ized trials. The Southwest Oncology Group (SWOG) conducted a randomize d trial comparing standard therapy, CHOP, to the third-generation chem otherapy regimens m-BACOD, ProMACE-CytaBOM, and MACOP-B. After 6 years , no difference in the response rate, progression-free survival, or ov erall survival has been found between CHOP and the third-generation re gimens. For example, the 6-year estimates of progression-free survival are CHOP 33%, m-BACOD 36%, ProMACE-CytaBOM 34%, and MACOP-B 32% (P = 0.31). The 6-year overall survival estimates are CHOP 42%, m-BACOD 40% , ProMACE-CytaBOM 46%, and MACOP-B 41% (P = 0.89). Furthermore, we hav e not identified any subset of patients who survive longer on treatmen t 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 desig ned to improve our ability to cure the disease. Examples of this inclu de (1) increasing the dose intensity of drugs used in standard regimen s and (2) autologous bone marrow transplantation and/or peripheral ste m-cell support as rescue from marrow-ablative chemotherapy. If a patie nt is not eligible or does not wish to participate in a clinical trial , CHOP, as inadequate as it is, remains the gold standard.