Chemotherapy Alone Compared With Chemotherapy Plus Radiotherapy for Localized Intermediate- And High-Grade non-Hodgkin's Lymphoma

N Engl J Med. 1998 Jul 2;339(1):21-6. doi: 10.1056/NEJM199807023390104.


Background: Patients with clinically localized, intermediate- or high-grade non-Hodgkin's lymphoma usually receive initial treatment with a doxorubicin-containing regimen such as cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP). Pilot studies suggest that eight cycles of CHOP alone or three cycles of CHOP followed by involved-field radiotherapy are effective in such patients.

Methods: We compared these two approaches in a prospective, randomized, multi-institutional study. The end points were progression-free survival, overall survival, and life-threatening or fatal toxic effects. Two hundred eligible patients were randomly assigned to receive CHOP plus radiotherapy, and 201 received CHOP alone.

Results: Patients treated with three cycles of CHOP plus radiotherapy had significantly better progression-free survival (P=0.03) and overall survival (P=0.02) than patients treated with CHOP alone. The five-year estimates of progression-free survival for patients receiving CHOP plus radiotherapy and for patients receiving CHOP alone were 77 percent and 64 percent, respectively. The five-year estimates of overall survival for patients receiving CHOP plus radiotherapy and for patients receiving CHOP alone were 82 percent and 72 percent, respectively. The adverse effects included one death in each treatment group. Life-threatening toxic effects of any type were seen in 61 of 200 patients treated with CHOP plus radiotherapy and in 80 of 201 patients treated with CHOP alone (P=0.06). The left ventricular function was decreased in seven patients who received CHOP alone, whereas no cardiac events were recorded in the group receiving CHOP plus radiotherapy (P=0.02).

Conclusions: Three cycles of CHOP followed by involved-field radiotherapy are superior to eight cycles of CHOP alone for the treatment of localized intermediate- and high-grade non-Hodgkin's lymphoma.

Publication types

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

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Combined Modality Therapy
  • Cyclophosphamide / administration & dosage
  • Cyclophosphamide / adverse effects
  • Disease-Free Survival
  • Doxorubicin / administration & dosage
  • Doxorubicin / adverse effects
  • Humans
  • Lymphoma, Non-Hodgkin / drug therapy*
  • Lymphoma, Non-Hodgkin / mortality
  • Lymphoma, Non-Hodgkin / pathology
  • Lymphoma, Non-Hodgkin / radiotherapy*
  • Middle Aged
  • Neoplasm Staging
  • Prednisone / administration & dosage
  • Prednisone / adverse effects
  • Proportional Hazards Models
  • Prospective Studies
  • Radiotherapy / adverse effects
  • Radiotherapy / mortality
  • Radiotherapy Dosage
  • Survival Analysis
  • Vincristine / administration & dosage
  • Vincristine / adverse effects


  • Vincristine
  • Doxorubicin
  • Cyclophosphamide
  • Prednisone

Supplementary concepts

  • CHOP protocol