Escalated as compared with standard doses of doxorubicin in BACOP therapy for patients with non-Hodgkin's lymphoma

N Engl J Med. 1993 Dec 9;329(24):1770-6. doi: 10.1056/NEJM199312093292404.

Abstract

Background and methods: In 1981 the Clinical Trials Group of the National Cancer Institute of Canada completed a pilot study in patients with advanced-stage non-Hodgkin's lymphoma with aggressive tumor histology. That study demonstrated the potential efficacy of escalating the dose of doxorubicin used in a regimen of bleomycin, doxorubicin, cyclophosphamide, vincristine, and prednisone (BACOP). In the present study, we compared standard BACOP (s-BACOP) with BACOP that included escalated doses of doxorubicin (esc-BACOP) in 238 patients 16 to 70 years old with previously untreated, advanced-stage intermediate- or high-grade non-Hodgkin's lymphoma. During the first 28-day cycle all patients received doxorubicin in a dose of 25 mg per square meter of body-surface area on days 1 and 8. Patients randomly assigned to receive s-BACOP subsequently received five identical cycles, whereas those assigned to receive esc-BACOP received 40 mg of doxorubicin per square meter on days 1 and 8 of five subsequent cycles if granulocytopenia (< 1000 cells per cubic millimeter) had not developed during the first cycle.

Results: The 119 patients assigned to the esc-BACOP regimen received doxorubicin at a significantly higher mean weekly dose intensity (13.5 vs. 10.4 mg per square meter per week, P < 0.001) and mean total dose (296 vs. 231 mg per square meter, P < 0.001). Because of granulocytopenia during the first cycle of therapy, only 56 of these patients (47 percent) received the escalated doses of doxorubicin. During a median follow-up of 65 months, there were no differences between the s-BACOP and esc-BACOP groups in response rate, overall survival, or survival without disease progression. When the patients who actually received the escalated doses of doxorubicin were compared with the patients in the s-BACOP group in whom neutropenia did not develop during the first treatment cycle, no difference between their outcomes was observed. Toxicity was greater in the esc-BACOP group.

Conclusions: In patients with advanced-stage intermediate- or high-grade non-Hodgkin's lymphoma, escalating the dose of doxorubicin in the BACOP regimen increases toxicity but does not improve the rate of response or survival.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bleomycin / administration & dosage
  • Bleomycin / adverse effects
  • Cyclophosphamide / administration & dosage
  • Cyclophosphamide / adverse effects
  • Dose-Response Relationship, Drug
  • Doxorubicin / administration & dosage*
  • Doxorubicin / adverse effects
  • Female
  • Follow-Up Studies
  • Humans
  • Lymphoma, Non-Hodgkin / drug therapy*
  • Lymphoma, Non-Hodgkin / mortality
  • Male
  • Middle Aged
  • Prednisone / administration & dosage
  • Prednisone / adverse effects
  • Prognosis
  • Treatment Outcome
  • Vincristine / administration & dosage
  • Vincristine / adverse effects

Substances

  • Bleomycin
  • Vincristine
  • Doxorubicin
  • Cyclophosphamide
  • Prednisone

Supplementary concepts

  • CHOP-B protocol