Taxane-based three-drug combination in metastatic and adjuvant treatment of breast cancer.

Considering the recommended dose of the docetaxel/doxorubicin combination (75 mg/m2 and 50 mg/m2, respectively), we decided to proceed with a pilot program in untreated metastatic breast cancer aimed at defining a multidrug regimen that could be later randomly compared with a standard doxorubicin-containing polychemotherapy regimen with equidoses of doxorubicin such as the FAC protocol (5-fluorouracil 500 mg/m2, doxorubicin 50 mg/m2, and cyclophosphamide 500 mg/m2) in first-line metastatic and adjuvant treatment of breast cancer patients. We proceeded with a pilot phase II study of the TAC combination, which consists of docetaxel 75 mg/m2 as a 1-hour infusion preceded by doxorubicin 50 mg/m2 and cyclophosphamide 500 mg/m2, both given as an intravenous bolus. Three hundred seventy courses were delivered in 54 anthracycline-naive patients, among whom 62% had visceral metastases. Median relative dose intensity was above 98% for all drugs. Grade 4 neutropenia was the main toxicity (70% of cycles) and the incidence of febrile neutropenia and infection was acceptable (6% and 0.8% of cycles, respectively). Acute and chronic extrahematologic toxicities were mild, mostly grade 2, and the docetaxel-specific toxicities (fluid retention, nail changes, etc) were not major clinical problems; no patient was discontinued due to fluid retention. The major response rate was 73% overall and 79% in measurable disease. Time to progression and survival are still under evaluation. The TAC combination is an active and well-tolerated regimen that is the basis of two currently open, pivotal, randomized phase III trials comparing TAC with FAC in the metastatic and adjuvant treatment of breast cancer.