Comparison of a second-generation combination chemotherapeutic regimen (m-BACOD) with a standard regimen (CHOP) for advanced diffuse non-Hodgkin's lymphoma

N Engl J Med. 1992 Nov 5;327(19):1342-9. doi: 10.1056/NEJM199211053271903.


Background: In 1984, the Eastern Cooperative Oncology Group began a randomized controlled clinical trial of patients with advanced (stage III or IV) diffuse mixed or diffuse large-cell lymphoma to determine whether complete-remission rates, survival, and toxicity differed when patients were treated with a chemotherapeutic regimen containing cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), as compared with a regimen containing bleomycin, doxorubicin, cyclophosphamide, vincristine, dexamethasone, methotrexate, and leucovorin (m-BACOD).

Methods: From July 1984 through January 1988, 392 patients were enrolled, 325 of whom (83 percent) were eligible for the analysis and capable of being evaluated. The extent of disease was defined according to standard staging techniques, including bilateral bone-core biopsies in 88 percent of patients. Randomization was stratified according to age (< 60 or > or = 60 years), performance status (0, 1, or other), stage (III or IV), and histologic presentation (diffuse mixed or diffuse large-cell lymphoma).

Results: After a median follow-up of four years, there were no significant differences in rates of complete remission, time to treatment failure, disease-free survival, or overall survival in the patients treated with CHOP as compared with those treated with m-BACOD. However, there was more severe and life-threatening pulmonary, infectious, and hematologic toxicity associated with the m-BACOD regimen. In an attempt to measure the importance of dose intensity in the 325 patients who could be analyzed, we retrospectively calculated dose intensity (measured in milligrams per square meter of body-surface area per week) and normalized dose intensity (defined as a percentage of the prescribed dose) for all drugs. The median normalized dose intensity for both cyclophosphamide and doxorubicin was found to be greater in the patients treated with CHOP than in those treated with m-BACOD.

Conclusions: For patients with stage III or IV diffuse mixed or diffuse large-cell lymphoma, CHOP is superior to m-BACOD, but the role of dose intensity is not yet clear.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Age Factors
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bleomycin / adverse effects
  • Bleomycin / therapeutic use
  • Cyclophosphamide / adverse effects
  • Cyclophosphamide / therapeutic use
  • Dexamethasone / adverse effects
  • Dexamethasone / therapeutic use
  • Doxorubicin / adverse effects
  • Doxorubicin / therapeutic use
  • Drug Administration Schedule
  • Female
  • Follow-Up Studies
  • Humans
  • Leucovorin / adverse effects
  • Leucovorin / therapeutic use
  • Lymphoma, Large B-Cell, Diffuse / drug therapy
  • Lymphoma, Non-Hodgkin / drug therapy*
  • Lymphoma, Non-Hodgkin / mortality
  • Lymphoma, Non-Hodgkin / pathology
  • Male
  • Methotrexate / adverse effects
  • Methotrexate / therapeutic use
  • Middle Aged
  • Prednisone / adverse effects
  • Prednisone / therapeutic use
  • Remission Induction
  • Survival Rate
  • Vincristine / adverse effects
  • Vincristine / therapeutic use


  • Bleomycin
  • Vincristine
  • Dexamethasone
  • Doxorubicin
  • Cyclophosphamide
  • Leucovorin
  • Prednisone
  • Methotrexate

Supplementary concepts

  • CHOP protocol
  • M-BACOD protocol