A multicentre phase II study of docetaxel 75 mg m-2 as first-line chemotherapy for patients with advanced breast cancer: report of the Clinical Screening Group of the EORTC. European Organization for Research and Treatment of Cancer.

In this phase II study, 39 women (median age 51 years) with advanced breast cancer received docetaxel (75 mg m-2) intravenously over 1 h every 3 weeks as first-line chemotherapy for advanced disease, without routine premedication for hypersensitivity reactions. In 31 evaluable patients, an overall response rate of 52% (95% CI 33-70%) was achieved, including a complete response rate of 13%. The median time to first response was 12 weeks (range 3-35+), the median duration of response was 34 weeks (range 11-42+) and the median time to progression was 24 weeks (range 0-42+). Docetaxel showed considerable activity in patients with visceral involvement (52% response), including lung (67%) and liver (44%) metastases. The safety profile was acceptable. Grade 4 neutropenia occurred in 82% of patients (53% of cycles); febrile neutropenia (grade 4 neutropenia with fever > 38 degrees C, requiring antibiotics) occurred in only three (7.7%) patients (1.4% of cycles) and none of these required hospitalisation. Acute adverse events were generally well tolerated, with only two grade 3 events and no grade 4 events reported. Despite no prophylactic premedication, the incidence of acute hypersensitivity reactions was only 13%. Fluid retention was widely experienced (72% of patients) but was severe in only five (12.8%) patients and was the reason for discontinuation of treatment in 16 patients. Nevertheless, patients were able to receive a median cumulative dose of approximately 592 mg m-2 before discontinuing treatment, and the syndrome was slowly reversible after treatment withdrawal. In conclusion, docetaxel, even at a dose of 75 mg m-2, is confirmed to be an active agent in breast cancer. Compared with an earlier study of first-line docetaxel at the usual dose of 100 mg-2, it appears that 75 mg m-2 produces a lower response rate (52% vs 68%), although this still compares favourably with that of doxorubicin monotherapy in a similar patient population (43%). This difference is particularly striking in subgroups of patients with particularly poor prognostic factors, such as liver metastases or involvement of more than two organs. The incidence of fluid retention appears to be similar at the two doses and, it is likely that premedication with corticosteroids will be preferable to dose reduction for managing this adverse event.