Dose-finding study of docetaxel and doxorubicin in first-line treatment ofpatients with metastatic breast cancer

Purpose: To determine the maximum tolerated dose (MTD), the dose-limiting t oxicity (DLT) and the recommended dose of docetaxel in combination with dox orubicin, and to evaluate the activity in patients with advanced breast can cer. Patients and methods: Forty-two women with untreated metastatic breast canc er (79% with visceral metastases; 52% with prior adjuvant anthracycline the rapy) were treated with doxorubicin (40-60 mg/m(2)) i.v. bolus followed one hour later by docetaxel (50-85 mg/m(2)) one-hour i.v. infusion every three weeks, without G-CSF support. Results: The MTD occurred at the dose level combining 85 mg/m(2) of docetax el and 50 mg/m(2) of doxorubicin, with the DLT being neutropenic sepsis. Ne utropenia and/or its complications were manageable and no grade 3-4 or seve re non-hematological toxicities were observed. Fluid retention was frequent but never severe. With a median cumulative dose of doxorubicin of 392 mg/m (2) (240-559 mg/m(2)) and a median follow-up time of 29 months (9+-41), no congestive heart failure was observed. High activity was observed at all do se levels, particularly the last four, with a response rate of 81% (95% con fidence interval (95% CI): 62.5-92.5). Median time to progression was 46 we eks (6+-62). Two-year survival was 66%, and median survival has not yet bee n reached. Conclusions: Docetaxel-doxorubicin is feasible, safe and highly active. The incidence of febrile neutropenia without G-CSF requires careful monitoring but is acceptable in this setting. There does not appear to be an increase in the cardiac toxicity of doxorubicin. The recommended dose is either doc etaxel 75 mg/m(2) and doxorubicin 50 mg/m(2) or docetaxel 60 mg/m(2) and do xorubicin 60 mg/m(2), administered every three weeks.