Final results of a randomized phase III trial comparing cyclophosphamide, epirubicin, and fluorouracil with a dose-intensified epirubicin and cyclophosphamide + filgrastim as neoadjuvant treatment in locally advanced breast cancer: an EORTC-NCIC-SAKK multicenter study.

Abstract

PURPOSE:

To compare the efficacy of a standard anthracycline-based regimen to a dose-intensified anthracycline regimen in locally advanced breast cancer.

PATIENTS AND METHODS:

Locally advanced breast cancer patients were randomly assigned onto a study comparing cyclophosphamide (C; 75 mg/m(2) orally days 1 to 14), epirubicin (E; 60 mg/m(2) intravenously [IV] days 1, 8), and fluorouracil (F; 500 mg/m(2) IV days 1, 8) six cycles every 28 days versus E (120 mg/m(2) IV day 1), C (830 mg/m(2) IV day 1), and granulocyte colony-stimulating factor (filgrastim; 5 micro g/kg/d subcutaneously days 2 to 13) six cycles every 14 days. The study was designed to detect a 15% improvement; that is, from 50% to 65% in median progression-free survival (PFS) in favor of the dose-intensified regimen.

RESULTS:

A total of 448 patients were enrolled over a period of 3 years. The median dose intensity delivered for C and E reached, respectively, 85% and 87% of that planned in the CEF arm and 96% and 95% of that planned in the EC arm. The dose-intensified arm was slightly more emetogenic and generated more grade 3 to 4 anemia but less febrile neutropenia episodes. After a median follow-up of 5.5 years, 277 events have been reported. The median PFS was 34 and 33.7 months for CEF and EC, respectively (P =.68), and the 5-year survival rate was 53% and 51% for CEF and EC, respectively (P =.94).

CONCLUSION:

Dose-intensified EC does not provide a measurable therapeutic benefit over CEF as neoadjuvant chemotherapy for unselected locally advanced breast cancer patients.

• Authors: P Therasse, L Mauriac, M Welnicka-Jaskiewicz, P Bruning, T Cufer, H Bonnefoi, E Tomiak, K I Pritchard, A Hamilton, M J Piccart, EORTC
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 21 Issue 5 Pg. 843-50 (Mar 01 2003) ISSN: 0732-183X [Print] United States
• PMID: 12610183 (Publication Type: Clinical Trial, Clinical Trial, Phase III, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Review)

Chemical References

• Recombinant Proteins
• Granulocyte Colony-Stimulating Factor
• Epirubicin
• Cyclophosphamide
• Filgrastim
• Fluorouracil

Topics

• Adolescent
• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Breast Neoplasms (drug therapy, economics, pathology)
• Costs and Cost Analysis
• Cyclophosphamide (administration & dosage, therapeutic use)
• Disease Progression
• Disease-Free Survival
• Dose-Response Relationship, Drug
• Epirubicin (administration & dosage, therapeutic use)
• Female
• Filgrastim
• Fluorouracil (therapeutic use)
• Granulocyte Colony-Stimulating Factor (therapeutic use)
• Humans
• Middle Aged
• Neoadjuvant Therapy
• Quality of Life
• Recombinant Proteins
• Survival Rate
• Treatment Outcome