PHASE-II STUDY OF HIGH-DOSE EPIRUBICIN IN COMBINATION WITH CYCLOPHOSPHAMIDE IN PATIENTS WITH ADVANCED BREAST-CANCER

Background: Combination chemotherapy for metastatic breast cancer will palliate symptoms in the majority of patients but only a small percen tage will have prolonged survival, Higher doses of doxorubicin lead to increased response rates in breast cancer and early studies have show n that epirubicin could be tolerated in higher doses with less relativ e toxicity than doxorubicin. Aims: This study was initiated to assess the dose of epirubicin that could be tolerated by escalating its dose while maintaining a fixed dose of cyclophosphamide. Simultaneously tum our response rate, spectrum of toxicities, duration of response and ov erall survival in patients with metastatic breast cancer were assessed . Methods: Patients with metastatic breast cancer commenced chemothera py with a starting dose of epirubicin of 120 milligram per metre squar ed (mg/m(2)) and cyclophosphamide 600 mg/m(2). The dose of epirubicin was to be escalated or reduced depending on toxicity. Results: Forty f emale patients were entered into this study and three patients withdre w because of toxicity. Overall tumour response rate was 75% with 27.5% of patients obtaining a complete response. Median time to progressive disease was 35 weeks and median overall survival was 48 weeks, with m edian survival for complete responders being 103 weeks. Thirty-one (77 %) patients completed five or more courses of treatment. Haematologica l toxicity was the main side effect and 70% of patients required a dos e reduction. No patients were eligible for a dose escalation. One pati ent died as a consequence of neutropenic sepsis. Four (10%) patients h ad treatment ceased because of decrease in left ventricular ejection f raction and one patient died as a consequence of heart failure. Four p atients remain alive. Conclusions: High dose epirubicin combined with cyclophosphamide is an effective treatment regimen for metastatic brea st cancer obtaining higher overall response rates with increased perce ntage complete responses compared to conventional dose chemotherapy. A lthough toxicity was increased, high dose chemotherapy was well tolera ted and mortality associated with treatment was not increased. No dose escalations of epirubicin were possible and a dose of 90 mg/m(2) of e pirubicin would be the maximum dose when used in combination with cycl ophosphamide. Further trials are required to determine the influence o f this high dose therapy on survival duration and whether comparable b enefits can be achieved with shorter durations of therapy.