Randomized Trial of High-dose Epirubicin and Cyclophosphamide x 3 Supported by Peripheral Blood Progenitor Cells Versus Anthracycline and Cyclophosphamide x 4 Followed by Cyclophosphamide, Methotrexate, and 5-fluorouracil x 3 as Adjuvant Treatment for High Risk Operable Stage ii and Stage Iii Breast Cancer in Premenopausal and Young Postmenopausal (Less Than or Equal to 65 Yrs) Patients.
OBJECTIVES: I. Compare the survival, disease-free survival, and systemic disease-free
survival of women with high-risk, operable stage II/III breast cancer treated with three
courses of dose-intensive epirubicin/cyclophosphamide (EC) supported by granulocyte
colony-stimulating factor (G-CSF) and G-CSF-mobilized peripheral blood stem cells vs.
standard EC followed by cyclophosphamide/methotrexate/fluorouracil. II. Compare the
toxicity, duration of quality-adjusted time without symptoms and toxicity, and quality of
life associated with these two treatments. III. Evaluate the cost effectiveness of these two
OUTLINE: This is a randomized study. Patients are stratified by estrogen receptor status and
menopausal status. Within 6 weeks of surgery, patients in the first group receive epirubicin
(preferred) or doxorubicin plus cyclophosphamide every 3 weeks for 4 courses followed by
conventional cyclophosphamide, methotrexate, and fluorouracil (CMF) every 4 weeks for 3
courses. Patients in the second group undergo stem cell mobilization and harvest with
granulocyte colony-stimulating factor (G-CSF) followed within 10 weeks of surgery by
high-dose chemotherapy with epirubicin and cyclophosphamide followed by peripheral blood
stem cell rescue and G-CSF. All patients receive adjuvant tamoxifen, and patients who
underwent lumpectomy prior to entry are required to receive adjuvant radiotherapy
(radiotherapy is optional for patients who underwent mastectomy prior to entry). Patients
are followed every 3 months for 2 years, then q 6 months for 3 years, then yearly.
PROJECTED ACCRUAL: 210 patients will be accrued over 4 years to provide 195 evaluable
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Time from randomization to recurrence (including recurrence isolated to the breast), metastasis, appearance of a second primary tumor, or death from any cause, whichever occurs first.
16 years after randomization.
Russell Basser, MD
United States: Federal Government