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Notes: Abstract Background:The combination of anthracyclines and taxanes iscurrently considered the first choice chemotherapy in advanced breast cancer(ABC) and considerable emphasis has been placed on programs exploring thesafest and most efficient way to integrate these classes of drugs in both themetastatic and, more recently, the adjuvant setting. We report here the overall results of the combination of epidoxorubicin (E)90 mg/m2 and docetaxel (D) 75 mg/m2 as first-linechemotherapy in ABC. Patients and methods:A total of 70 patients were entered in theinitial dose-finding study (20 patients) and in the subsequent extended phaseII trial (50 patients). Overall 54% of patients had dominant visceraldisease and 57% had at least two metastatic sites. Adjuvantanthracyclines were allowed in the phase II part of the study based on thelack of cardiac toxicity observed in the phase I study at a median cumulativeE dose of 480 mg/m2. A maximum of eight cycles of the combinationwas allowed, and cardiac function was monitored at baseline and after everysecond course by echocardiography. Results:Overall, the median number of cycles administered withthe combination was 4 (range 3–8). Neutropenia was confirmed to be themain haematological toxicity, with granulocyte colony-stimulating factor(G-CSF) support required in 44% of the cycles. Febrile neutropeniaoccurred in 12% of cycles of the combination but 52% of theepisodes could be managed on an outpatient basis with oral antibiotics.Overall, the median cumulative dose of E, including prior adjuvantanthracyclines, was 495 mg/m2 (range 270–1020mg/m2). One patient who received adjuvant E together withradiotherapy to the left chest wall developed fully reversible clinical signsof cardiotoxicity and a significant decrease of LVEF to 35% after acumulative E dose of 870 mg/m2, with four additional patients(6%) developing asymptomatic and transient decline of resting LVEF. Theoverall response rate (ORR) in 68 evaluable patients was 66%(95% confidence interval (95% CI): 54%–73%).A comparable antitumour activity of 71% was reported in the group ofpatients with a prior adjuvant chemotherapy with anthracyclines. After anoverall median follow-up time of 22 months (range 4–39+), the mediantime to progression (TTP) was 4.5 months and the median duration of responsewas 8 months (range 3–16). No pharmacokinetic (Pk) interaction could bedemonstrated between E and D when given simultaneously and sequentially witha one-hour interval. Conclusions:The combination of E and D in a multi-institutionalsetting is an active and safe regimen in poor- prognosis patients with ABC.New combinations and schedules are worth considering in an attempt to furtherimprove disease response and long-term control of the disease.