Trial Information

Adjuvant Treatment of Biologically Aggressive Breast Cancer (N-,N+1,3): Controlled Clinical Study

OBJECTIVES:

Primary

- To determine the impact of adjuvant chemotherapy comprising epirubicin hydrochloride
followed by cyclophosphamide, methotrexate, and fluorouracil versus cyclophosphamide,
methotrexate, and fluorouracil followed by epirubicin hydrochloride versus
cyclophosphamide, methotrexate, and fluorouracil on overall survival of patients with
biologically aggressive, resectable, node-negative or node-positive breast cancer.

Secondary

- To assess the disease-free survival and patterns of relapse in these patients.

- To assess the tolerance to and toxicity of treatment in these patients.

- To determine the quality of life of these patients.

- To verify the effectiveness of these treatments in different subgroups of patients.

- To collect, retrospectively, information on the expression of tumor suppressor gene
p53, oncogene c-erbB-2, and bcl-2 protein involved in apoptosis. (exploratory)

OUTLINE: This is a multicenter study. Patients are stratified according to center, lymph
node status (N0 vs N1-3), and estrogen receptor status (negative vs positive). Patients are
randomized to 1 of 3 treatment arms.

- Arm I: Beginning 4-6 weeks following surgery, patients receive epirubicin hydrochloride
IV on day 1. Treatment repeats every 3 weeks for 4 courses. Patients then receive
cyclophosphamide IV, methotrexate IV, and fluorouracil IV on days 1-8. Treatment
repeats every 4 weeks for 4 courses.

- Arm II: Beginning 4-6 weeks following surgery, patients receive cyclophosphamide IV,
methotrexate IV, and fluorouracil IV on days 1-8. Treatment repeats every 4 weeks for 4
courses. Patients then receive epirubicin hydrochloride IV on day 1. Treatment repeats
every 3 weeks for 4 courses.

- Arm III (closed to accrual as of 12/7/2009): Beginning 4-6 weeks following surgery,
patients receive cyclophosphamide IV, methotrexate IV, and fluorouracil IV on days 1-8.
Treatment repeats every 4 weeks for 6 courses.

Patients with estrogen receptor-positive disease receive tamoxifen daily for 5 years after
completing chemotherapy.

After completion of study therapy, patients are followed every 3 months for 1 year, every 6
months for 4 years, and then annually for 5 years.