Dose-intensive epirubicin-based chemotherapy is superior to an intensive intravenous cyclophosphamide, methotrexate, and fluorouracil regimen in metastatic breast cancer: a randomized multinational study.

Abstract

PURPOSE:

To determine the relative efficacy of a cyclophosphamide epirubicin and fluorouracil (CEF) regimen compared with an intravenous (IV) cyclophosphamide, methotrexate, and fluorouracil (CMF) combination in metastatic breast cancer.

PATIENTS AND METHODS:

Patients were randomized to receive either CEF (cyclophosphamide 400 mg/m(2) IV, epirubicin 50 mg/m(2) IV, and fluorouracil 500 mg/m(2) IV on days 1 and 8), or CMF (cyclophosphamide 500 mg/m(2) IV, methotrexate 40 mg/m(2) IV, and fluorouracil 600 mg/m(2) IV on days 1 and 8). Treatment was given in 3- to 4-week cycles for a total of six to nine cycles.

RESULTS:

A total of 460 patients (223 CEF and 237 CMF) were randomized. Overall response rate was superior for CEF than CMF in all randomized patients (57% v 46%, respectively; P =.01) and in the assessable subset (66% v 52%, respectively; P =.005). With a median follow-up of more than 20 months, time to progression (TTP) was significantly longer with CEF than CMF (median 8.9 v 6.3 months, respectively; P =.0064), as was time to treatment failure (TTF) (median 6.2 v 5.0 months, respectively; P =.01). Significant survival differences were not observed between CEF and CMF (median 20.1 v 18.2 months, respectively; P =.23). Granulocytopenia and infections were similar in both arms. Grade 3/4 nausea/vomiting and alopecia were more frequent with CEF, whereas diarrhea was more frequent with CMF. Cardiac toxicity, primarily asymptomatic, required withdrawal from study of 15 patients on CEF (7%) and one patient on CMF.

CONCLUSION:

This CEF regimen safely provides significantly better tumor control than CMF, manifest as a higher response rate, and longer TTP and TTF, but not survival, when used as first-line chemotherapy for metastatic breast cancer.

• Authors: S P Ackland, A Anton, G P Breitbach, E Colajori, J M Tursi, C Delfino, A Efremidis, A Ezzat, A Fittipaldo, K Kolaric, M Lopez, D Viaro, HEPI 013 study group
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 19 Issue 4 Pg. 943-53 (Feb 15 2001) ISSN: 0732-183X [Print] United States
• PMID: 11181656 (Publication Type: Clinical Trial, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Cytarabine
• Epirubicin
• Cyclophosphamide
• Cisplatin
• Fluorouracil
• Methotrexate

Topics

• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage, adverse effects)
• Breast Neoplasms (drug therapy, mortality)
• Cisplatin (administration & dosage, adverse effects)
• Cyclophosphamide (administration & dosage, adverse effects)
• Cytarabine (administration & dosage, adverse effects)
• Disease-Free Survival
• Drug Administration Schedule
• Epirubicin (administration & dosage, adverse effects)
• Female
• Fluorouracil (administration & dosage, adverse effects)
• Humans
• Injections, Intravenous
• Methotrexate (administration & dosage, adverse effects)
• Middle Aged
• Neoplasm Metastasis
• Survival Analysis