PHASE-II TRIAL OF HIGH-DOSE EPIRUBICIN AND CYCLOPHOSPHAMIDE IN ADVANCED BREAST-CANCER

Between February 1990 and December 1991 high-dose epirubicin (Epi)(120 mg/m(2)) plus cyclophosphamide (CTX)(600 mg/m(2)) were given every 3 weeks to 52 patients with locally advanced and metastatic breast cance r. 26 patients with locally advanced disease received four courses of this regimen before and after local treatments. 26 patients had metast atic disease: they received eight courses unless progression or unacce ptable toxicity occurred. Responses were seen in 37/48 (77%) evaluable patients including 14 complete responses (CR), 23 partial responses ( PR), nine stable disease, two progressive disease. Among the 25 evalua ble patients with locally advanced disease, 9 had a CR and 11 a > 80% decrease in tumour volume. 6 patients (24%) had a pathologically confi rmed complete response. 18 patients (72%) had a tumour reduction to 0- 2 cm. The 3-year disease-free survival was 60%. Of the 23 evaluable pa tients with metastatic disease, 5 obtained a CR and 10 a PR, yielding an overall response rate of 65%. Myelosuppression was substantial with a grade 3-4 leucopenia in 76% of the patients even if neutropenic fev er occurred in only 7% of the courses. A clinical congestive heart fai lure occurred in 1 patient following a total Epi dose of 960 mg/m(2) a nd a bilateral quadrantectomy and radiotherapy. We conclude that (1) h igh-dose Epi + CTX is a very active regimen, in particular for the pat ients with locally advanced breast cancer; (2) breast conservation aft er this regimen in some of these patients may be considered; (3) neutr openia is the dose-limiting toxicity. Currently, a phase II study usin g the same combination given every 2 weeks together with r-methuG-CSF is ongoing.