Standard chemotherapy with or without high-dose chemotherapy for aggressive non-Hodgkin's lymphoma: randomized phase III EORTC study.

Abstract

BACKGROUND:

The long-term outcome for patients with aggressive non-Hodgkin's lymphoma (NHL) is poor. Consequently, the European Organization for Research and Treatment of Cancer Lymphoma Group designed a prospective randomized trial to investigate whether high-dose chemotherapy plus autologous bone marrow transplantation (ABMT) after standard combination chemotherapy improves long-term survival.

METHODS:

Patients aged 15-65 years with aggressive NHL received three cycles of CHVmP/BV polychemotherapy (i.e., a combination of cyclophosphamide, doxorubicin, teniposide, and prednisone, with bleomycin and vincristine added at mid-cycle). After these three cycles, patients with a complete or partial remission and at that time no lymphoma involvement in the bone marrow were randomly assigned to the ABMT arm (a further three cycles of CHVmP/BV followed by BEAC [i.e., a combination of carmustine, etoposide, cytarabine, and cyclophosphamide] chemotherapy and ABMT) or to the control arm (five more cycles of CHVmP/BV). All statistical tests are two-sided.

RESULTS:

From December 1990 through October 1998, 311 patients (median age = 44 years) were registered and received the first three cycles of CHVmP/BV, and 194 patients were randomly assigned to the treatment arms. Approximately 70% (140 patients) of these patients were of low or low-intermediate International Prognostic Index (IPI) risk. After a median follow-up of 53 months, an intention-to-treat analysis showed a time to disease progression and overall survival at 5 years of 61% (95% confidence interval [CI] = 51% to 72%) and 68% (95% CI = 57% to 79%), respectively, for the ABMT arm and 56% (95% CI = 45% to 67%) and 77% (95% CI = 67% to 86%), respectively, for the control arm. Differences between arms were not statistically significant. A subset analysis on IPI risk groups, although too small for reliable statistical analysis, yielded similar results.

CONCLUSIONS:

Standard combination therapies remain the best choice for most patients with aggressive NHL. We recommend that patients with IPI low or low-intermediate risk not be subjected to high-dose chemotherapy and ABMT as a first-line therapy.

• Authors: H C Kluin-Nelemans, V Zagonel, A Anastasopoulou, D Bron, K J Roozendaal, E M Noordijk, H Musson, I Teodorovic, B Maes, A Carbone, P Carde, J Thomas
• Journal: Journal of the National Cancer Institute (J Natl Cancer Inst) Vol. 93 Issue 1 Pg. 22-30 (Jan 03 2001) ISSN: 0027-8874 [Print] United States
• PMID: 11136838 (Publication Type: Clinical Trial, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Bleomycin
• Vincristine
• Doxorubicin
• Cyclophosphamide
• Teniposide
• Prednisone

Topics

• Adolescent
• Adult
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage, adverse effects, therapeutic use)
• Bleomycin (administration & dosage)
• Cause of Death
• Cyclophosphamide (administration & dosage)
• Doxorubicin (administration & dosage)
• Drug Administration Schedule
• Europe
• Female
• Hematopoietic Stem Cell Transplantation
• Humans
• Lymphoma, Non-Hodgkin (drug therapy, radiotherapy, therapy)
• Male
• Middle Aged
• Prednisone (administration & dosage)
• Prospective Studies
• Radiotherapy, Adjuvant
• Survival Analysis
• Teniposide (administration & dosage)
• Transplantation, Autologous
• Treatment Outcome
• Vincristine (administration & dosage)