Epidoxorubicin and docetaxel as first-line chemotherapy in patients with advanced breast cancer: A multicentric phase I-II study

Background: The combination of anthracyclines and taxanes is currently cons idered the first choice chemotherapy in advanced breast cancer (ABC) and co nsiderable emphasis has been placed on programs exploring the safest and mo st efficient way to integrate these classes of drugs in both the metastatic and, more recently, the adjuvant setting. We report here the overall results of the combination of epidoxorubicin (E) 90 mg/m(2) and docetaxel (D) 75 mg/m(2) as first-line chemotherapy in ABC. Patients and methods: A total of 70 patients were entered in the initial do se-finding study (20 patients) and in the subsequent extended phase II tria l (50 patients). Overall 54% of patients had dominant visceral disease and 57% had at least two metastatic sites. Adjuvant anthracyclines were allowed in the phase II part of the study based on the lack of cardiac toxicity ob served in the phase I study at a median cumulative E dose of 480 mg/m(2). A maximum of eight cycles of the combination was allowed, and cardiac functi on was monitored at baseline and after every second course by echocardiogra phy. Results: Overall, the median number of cycles administered with the combina tion was 4 (range 3-8). Neutropenia was confirmed to be the main haematolog ical toxicity, with granulocyte colony-stimulating factor (G-CSF) support r equired in 44% of the cycles. Febrile neutropenia occurred in 12% of cycles of the combination but 52% of the episodes could be managed on an outpatie nt basis with oral antibiotics. Overall, the median cumulative dose of E, i ncluding prior adjuvant anthracyclines, was 495 mg/m(2) (range 270-1020 mg/ m(2)). One patient who received adjuvant E together with radiotherapy to th e left chest wall developed fully reversible clinical signs of cardiotoxici ty and a significant decrease of LVEF to 35% after a cumulative E dose of 8 70 mg/m(2), with four additional patients (6%) developing asymptomatic and transient decline of resting LVEF. The overall response rate (ORR) in 68 ev aluable patients was 66% (95% confidence interval (95% CI): 54%-73%). A com parable antitumour activity of 71% was reported in the group of patients wi th a prior adjuvant chemotherapy with anthracyclines. After an overall medi an follow-up time of 22 months (range 4-39+), the median time to progressio n (TTP) was 4.5 months and the median duration of response was 8 months (ra nge 3-16). No pharmacokinetic (Pk) interaction could be demonstrated betwee n E and D when given simultaneously and sequentially with a one-hour interv al. Conclusions: The combination of E and D in a multi-institutional setting is an active and safe regimen in poor- prognosis patients with ABC. New combi nations and schedules are worth considering in an attempt to further improv e disease response and long-term control of the disease.