Abstract
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 adjuvant therapy. A combined modality regimen that includes anthracyclin-based chemotherapy, high-dose chemotherapy with peripheral stem cell support and radiation and hormonal therapy is currently under investigation in this subset of patients. The present study aims to document the efficacy and feasibility of dose-intensive epidoxorubicin in combination with a standard dose of 5-fluorouracil and cyclophosphamide as up-front chemotherapy in this setting. A preoperative chemotherapy regimen consisting of three courses of 5-fluorouracil 500 mg m-2, epidoxorubicin 120 mg m-2 and cyclophosphamide 500 mg m-2 (FE120C) was administered 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. Sixty-six patients were evaluable for clinical response and histopathological examination could be performed in 62 of these. Thirteen patients achieved a clinical complete response (20%). Of these patients, microscopic examination of the mastectomy specimen revealed absence of malignant cells in two and exclusively ductal carcinoma in situ (DCIS) in another two patients. In addition, of the 46 patients (70%) with a clinical partial response, at pathological examination one patient had sclerosis only and four had DCIS. This results in a pathological complete response in three (5%) of all patients and absence of invasive carcinoma in 10%. None of the patients progressed during chemotherapy. The major toxicity was moderate bone marrow suppression with a median white blood count (WBC) nadir of 1800 microliters-1 (range 500-4900). Other toxicities were mild. The full planned dose could be given without delays in 66 of 70 patients FE120C is well tolerated and is highly effective as up-front chemotherapy in relatively young patients with high-risk breast cancer, with a 90% (CI 74-98%) clinical objective response rate.
Highlights
In an attempt to improve the outlook for patients with apical node-positive stage III breast carcinoma, we have developed a combined modality regimen incorporating preoperative chemotherapy followed by surgery, high-dose chemotherapy with autotransplantation, radiation therapy and hormonal therapy (Figure 1)
Four patients had undergone a mastectomy with axillary node dissection elsewhere, at which time tumour spread to the apical lymph nodes had been found
ADCIS, ductal carcinoma in situ. bFollowing up-front FE120C, in one patient the primary tumour contained only one small focus of DCIS; two of the seven axillary lymph nodes showed invasive carcinoma. cln three patients pathological examination revealed a complete response in the breast; small foci of invasive carcinoma were observed in the axillary lymph nodes only. dFour patients refused surgery
Summary
To be eligible for the study patients had to meet the following criteria: histologically or cytologically documented epithelial carcinoma of the breast with apical axillary lymph node metastases at exploration, i.e. stage IIA- IIIB disease but otherwise operable according to the Haagensen criteria. If the WBC was 3000 dl-1 or less at day 21 or the platelet count below 100 000 dl-', retreatment was delayed for a week If after this week recovery had occurred, a full dose of all three agents was administered. If the WBC was even lower or if the platelet count remained less than 100 000 ,ul-1, the patient was taken off study. Antiemetics were employed both prophylactically and as needed, and consisted of 5 HT-3 antagonists with or without dexamethasone. Patients considered to have clinically 'FECresponsive' tumours were subsequently randomised in a second study, in which the curative potential of dose intensification with peripheral blood progenitor cell support, followed by surgery, radiotherapy and hormonal treatment are investigated (Figure 1). Toxicity and efficacy data of the high-dose chemotherapy regimen, consisting of cyclophosphamide, thiotepa and carboplatin (CTC), have been reported previously (Rodenhuis et al, 1992; van der Wall et al, 1995)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
