Recombinant interferon alfa-2b combined with a regimen containing doxorubicin in patients with advanced follicular lymphoma. Groupe d'Etude des Lymphomes de l'Adulte

N Engl J Med. 1993 Nov 25;329(22):1608-14. doi: 10.1056/NEJM199311253292203.


Background: Interferon alfa and cytotoxic drugs have synergistic effects in patients with non-Hodgkin's lymphoma. In 1986, we designed a clinical trial to evaluate the benefit of concomitant administration of recombinant interferon alfa with a regimen containing doxorubicin in patients with follicular non-Hodgkin's lymphoma.

Methods: The trial involved 242 patients with advanced low-grade follicular non-Hodgkin's lymphoma selected on the basis of clinical, radiographic, and biologic criteria. All patients were treated with a regimen consisting of cyclophosphamide, doxorubicin, teniposide, and prednisone (CHVP), given monthly for six cycles and then every two months for one year. After randomization, 123 patients also received interferon alfa-2b at a dosage of 5 million units three times weekly for 18 months. The remaining 119 patients received chemotherapy alone.

Results: As compared with the patients treated with CHVP only, the patients treated with CHVP plus interferon alfa had a higher overall rate of response (85 percent vs. 69 percent, P = 0.006), a longer median event-free survival (34 months vs. 19 months, P < 0.001), and a higher rate of survival at 3 years (86 percent vs. 69 percent, P = 0.02). Granulocyte toxicity was greater in the patients treated with CHVP plus interferon alfa than in those treated with CHVP alone. There were no treatment-related deaths. Interferon alfa had to be stopped because of toxic effects (fatigue and hepatitis) in 13 patients (11 percent).

Conclusions: The addition of interferon alfa to a regimen containing doxorubicin increased the rate of response, event-free survival, and overall survival in patients with advanced follicular non-Hodgkin's lymphoma, without serious toxicity, although some patients were unable to tolerate the side effects.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Confidence Intervals
  • Cyclophosphamide / administration & dosage
  • Cyclophosphamide / therapeutic use
  • Doxorubicin / administration & dosage
  • Doxorubicin / therapeutic use
  • Female
  • Humans
  • Interferon alpha-2
  • Interferon-alpha / adverse effects
  • Interferon-alpha / therapeutic use*
  • Lymphoma, Follicular / drug therapy*
  • Lymphoma, Follicular / mortality
  • Male
  • Middle Aged
  • Prednisone / administration & dosage
  • Prednisone / therapeutic use
  • Prospective Studies
  • Recombinant Proteins
  • Regression Analysis
  • Survival Rate
  • Teniposide / administration & dosage
  • Teniposide / therapeutic use


  • Interferon alpha-2
  • Interferon-alpha
  • Recombinant Proteins
  • Doxorubicin
  • Cyclophosphamide
  • Teniposide
  • Prednisone

Supplementary concepts

  • CHVP protocol