High-dose epirubicin plus docetaxel at standard dose with lenograstim support as first-line therapy in advanced breast cancer

On the basis of preclinical and clinical data, we designed a phase II study to determine the efficacy and feasibility of high-dose epirubicin plus doc etaxel (Taxotere) with lenograstim support, as first-line therapy for patie nts with advanced breast cancer. Patients with histologic evidence of metas tatic breast cancer, without previous chemotherapy, adequate organ function s, Eastern Cooperative Oncology Group performance status less than 2, and s igned informed consent entered in the trial. Treatment consisted of premedi cation the day before the treatment day for 3 consecutive days (dexamethaso ne 16 mg o.r. and 5-HT3 antagonists). On the treatment day 1, epirubicin 13 0 mg/m(2) was administered as a 15-minute intravenous infusion followed 1 h our later by 1-hour intravenous infusion of docetaxel 100 mg/m(2). Cycles w ere repeated every 21 days, for a maximum of 8 cycles. Lenograstim (5 mug/k g, s.c.) was started 48 hours later (day 4) and was given daily for 10 cons ecutive days. Response evaluation was made after the third cycle was applie d, following World Health Organization criteria. Responding patients receiv ed five additional cycles. Median time to progression and survival were cal culated according to the Kaplan-Meier method. A total of 32 patients have b een included in the study. A total of 236 courses were delivered. A total r esponse rate of 87.5% (95% confidence interval [CI] of 77-98) was obtained. There were 11 complete responses and 17 partial responses. Toxicity was mi ld, with a low incidence of undesirable effects (7 cycles, 2.9% were delaye d from 3 to 6 days because of neutropenia). After a median follow-up time o f 490 days (range, 131-966 days), the median time to progression was 490 da ys (95% CI 314-575), and the median survival was 604 days (95% CI 513-785). This epirubicin plus docetaxel regimen is an efficient treatment for patie nts with advanced breast canter. The lenograstim support allows the adminis tration of such a chemotherapy regimen with a modest incidence of side effe cts. A larger number of patients need to be evaluated.