Dose-dense sequential adjuvant chemotherapy with epirubicin, paclitaxel and CMF in high-risk breast cancer

Dose-dense sequential chemotherapy appears to be a promising approach in th e management of patients with operable breast cancer. We evaluated the tole rability of such a novel chemotherapeutic regimen in high-risk patients. Fr om February 1995 until September 1997, 49 women with histologically confirm ed breast cancer and greater than or equal to 10 involved axillary nodes we re treated postoperatively with three cycles of epirubicin (110 mg/m(2)) fo llowed by three cycles of paclitaxel (250 mg/m(2) in a 3-hour infusion) fol lowed by three cycles of 'intensified' CMF (cyclophosphamide 840 mg/m(2), m ethotrexate 57 mg/m(2), fluorouracil 840 mg/m(2); E-T-CMF). All cycles were repeated every 2 weeks with G-CSF support. Ovarian ablation with monthly i njections of triptorelin for 1 year was performed in premenopausal patients and tamoxifen was prescribed for 5 years to all women with positive recept or status after the completion of chemotherapy. A total of 456 cycles of ch emotherapy were administered, 363 (80%) of them at fu II dose. Forty-seven (96%) patients received all 9 cycles of chemotherapy. Relative dose intensi ty of epirubicin was 0.98, of paclitaxel 0.97, of cyclophosphamide 0.99, of methotrexate 0.98 and of fluorouracil 0.99. Grade 3-4 toxicities included anemia (8%), leukopenia (8%), peripheral neuropathy (6%), neutropenia (4%), thrombocytopenia (4%), stomatitis (2%), diarrhea (2%), fatigue (2%) and hy persensitivity reaction (2%). Febrile neutropenia occurred in 2 patients. A lopecia was universal. After a median follow-up of 3 years, 11 women (22%) relapsed and 4 (8%) died. The 3-year actuarial disease-free survival rate w as 72% and the 3-year overall survival rate 90%. The E-T-CMF regimen is wel l tolerated, as adjuvant treatment, in patients with operable breast cancer with promising activity and deserves further evaluation in phase III studi es. Copyright (C) 2001 S.Karger AG, Basel.