EFFICACY OF UP-FRONT 5-FLUOROURACIL-EPIDOXORUBICIN-CYCLOPHOSPHAMIDE (FEC) CHEMOTHERAPY WITH AN INCREASED DOSE OF EPIDOXORUBICIN IN HIGH-RISK BREAST-CANCER PATIENTS

The prognosis of patients with stage IIIB breast carcinoma with tumour spread to the apical axillary lymph nodes has hardly improved despite adequate locoregional control and the introduction of systemic adjuva nt therapy. A combined modality regimen that includes anthracyclin-bas ed chemotherapy, high-dose chemotherapy with peripheral stem cell supp ort and radiation and hormonal therapy is currently under investigatio n in this subset of patients. The present study aims to document the e fficacy and feasibility of dose-intensive epidoxorubicin in combinatio n with a standard dose of 5-fluorouracil and cyclophosphamide as up-fr ont chemotherapy in this setting. A preoperative chemotherapy regimen consisting of three courses of 5-fluorouracil 500 mg m(-2), epidoxorub icin 120 mg m(-2) and cyclophosphamide 500 mg m(-2) (FE(120)C) was adm inistered at 21 day intervals without haematopoietic growth factors to 70 patients with apex node-positive disease. All patients were below 60 years of age and had not had prior chemotherapy or radiotherapy. Si xty-six patients were evaluable for clinical response and histopatholo gical examination could be performed in 62 of these. Thirteen patients achieved a clinical complete response (20%). Of these patients, micro scopic examination of the mastectomy specimen revealed absence of mali gnant cells in two and exclusively ductal carcinoma in situ (DCIS) in another two patients. In addition, of the 46 patients (70%) with a cli nical partial response, at pathological examination one patient had sc lerosis only and four had DCIS. This results in a pathological complet e response in three (5%) of all patients and absence of invasive carci noma in 10%. None of the patients progressed during chemotherapy. The major toxicity was moderate bone marrow suppression with a median whit e blood count (WBC) nadir of 1800 mu l(-1) (range 500-4900). Other tox icities were mild. The full planned dose could be given without delays in 66 of 70 patients. FE(120)C is well tolerated and is highly effect ive as up-front chemotherapy in relatively young patients with high-ri sk breast cancer, with a 90% (CI 74-98%) clinical objective response r ate.