A multicentre phase II study of the efficacy and safety of docetaxel as first-line treatment of advanced breast cancer: report of the Clinical Screening Group of the EORTC.

BACKGROUND: Two previous phase II trials of docetaxels as first line chemotherapy of advanced breast cancer have been conducted by the Clinical Screening Group of the EORTC. In these 2 studies, docetaxel 100 mg/m2 and 75 mg/m2 were administered without routine premedication and produced overall response rates of 68% and 52% respectively. Fluid retention was the most problematic adverse event in these 2 studies in which premedication was not routinely administered. This study investigated the efficacy and safety profile of docetaxel with a 1-day prophylactic premedication. PATIENTS AND METHODS: Docetaxel 100 mg/m2 was administered intravenously over 1 hour, every 3 weeks, to 37 women (aged 29-65 years) with advanced breast cancer. A 1-day regimen of intravenous antihistamine and oral corticosteroids was given with each dose. Full doses of docetaxel were administered in 179 of 200 cycles (89.5%), giving a median relative dose intensity of 0.98.
RESULTS: Tumour regression was achieved in 25 patients (7.66%) after a median of 7 weeks, and 2 patients (5.4%) had a complete response. Response rates were 67.9% in patients with visceral metastases, 76.9% in liver metastases and 83.3% in patients with > 2 organs involved. The median time to progression was 31 weeks (range 1-36+). After a median follow-up time of 6.9 months (range 4.6-9.4), 31 patients (83.7%) were still alive. The most common adverse events (AE) were neutropenia (97%), alopecia (97%, grade 1-2), fluid retention (89%, mainly mild to moderate) and neurosensory disorders (81%, mainly mild to moderate). Only 5 patients experienced febrile neutropenia requiring hospitalisation and/or antibiotic therapy. Sixteen patients discontinued treatment because of fluid retention; nevertheless, 13 of these achieved an objective antitumour response and none had any significant deterioration in performance status. AEs were generally reversible and easily managed, and there were no deaths attributable to docetaxel-related AEs.
CONCLUSIONS: Docetaxel produces very effective tumour response with acceptable tolerability when used as first-line chemotherapy in patients with advanced breast cancer. The 1-day premedication regimen used in this study was less effective in reducing the incidence and severity or delaying the onset of fluid retention than the currently recommended 5-day corticosteroid premedication. The optimum premedication regimen remains to be defined.