Accelerated-intensified cyclophosphamide, epirubicin, and fluorouracil (CEF) compared with standard CEF in metastatic breast cancer patients: results of a multicenter, randomized phase III study of the Italian Gruppo Oncologico Nord-Ouest-Mammella Inter Gruppo Group.

Abstract

PURPOSE:

To evaluate whether an accelerated-intensified cyclophosphamide, epirubicin, and fluorouracil (CEF) chemotherapy regimen with the support of granulocyte colony-stimulating factor (G-CSF) induces a higher activity and efficacy compared with standard CEF in metastatic breast cancer patients.

PATIENTS AND METHODS:

Stage IV breast cancer patients were randomized to receive as first-line chemotherapy either standard CEF (cyclophosphamide 600 mg/m(2), epirubicin 60 mg/m(2), and fluorouracil 600 mg/m(2)) administered every 21 days (CEF21) or accelerated-intensified CEF (cyclophosphamide 1,000 mg/m(2), epirubicin 80 mg/m(2), and fluorouracil 600 mg/m(2)) administered every 14 days (HD-CEF14) with the support of G-CSF. Treatment was administered for eight cycles.

RESULTS:

A total of 151 patients were randomized (74 patients on the CEF21 arm and 77 on the HD-CEF14 arm). In both arms, the median number of administered cycles was eight. The dose-intensity actually administered was 93% and 86% of that planned, in CEF21- and HD-CEF14-treated patients, respectively. Compared with the CEF21 arm, the dose-intensity increase in the HD-CEF14 arm was 80%. Both nonhematologic and hematologic toxicities were higher in the HD-CEF14 arm than in the CEF21 arm. During chemotherapy, four deaths occurred in the HD-CEF14 arm. No difference in overall response rate (complete plus partial responses) was observed: 49% and 51% in the CEF21 and HD-CEF14 arms, respectively (P =.94). A slightly non-statistically significant higher percentage of complete response was observed in the HD-CEF14 arm (20% v 15%). No difference in efficacy was observed. The median time to progression was 14.3 and 12.8 months in the CEF21 and HD-CEF14 arms, respectively (P =.69). Median overall survival was 32.7 and 27.2 months in the CEF21 and HD-CEF14 arms, respectively (P =.16).

CONCLUSION:

In metastatic breast cancer patients, an 80% increase in dose-intensity of the CEF regimen, obtained by both acceleration and dose intensification, does not improve the activity and the efficacy compared with a standard dose-intensity CEF regimen.

• Authors: L Del Mastro, M Venturini, R Lionetto, F Carnino, D Guarneri, L Gallo, A Contu, P Pronzato, L Vesentini, M Bergaglio, S Comis, R Rosso
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 19 Issue 8 Pg. 2213-21 (Apr 15 2001) ISSN: 0732-183X [Print] United States
• PMID: 11304774 (Publication Type: Clinical Trial, Clinical Trial, Phase III, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Granulocyte Colony-Stimulating Factor
• Epirubicin
• Cyclophosphamide
• Fluorouracil

Topics

• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage, therapeutic use)
• Breast Neoplasms (drug therapy, pathology)
• Cyclophosphamide (administration & dosage)
• Disease Progression
• Disease-Free Survival
• Dose-Response Relationship, Drug
• Drug Administration Schedule
• Epirubicin (administration & dosage)
• Female
• Fluorouracil (administration & dosage)
• Granulocyte Colony-Stimulating Factor (administration & dosage)
• Humans
• Male
• Middle Aged
• Neoplasm Metastasis
• Treatment Outcome