Phase III Trial Comparing Three Doses of Docetaxel for Second-Line Treatment of Advanced Breast Cancer

Purpose To evaluate whether a relationship exists between docetaxel dose and clinical response in the treatment of patients with advanced breast cancer. Patients and Methods Patients whose cancer had progressed after one prior chemotherapy regimen for advanced breast cancer or had recurred during or within 6 months of adjuvant chemotherapy were randomly assigned to docetaxel 60, 75, or 100 mg/m 2 intravenously every 3 weeks. Results Five hundred twenty-seven patients were randomly assigned (intent to treat [ITT]), and 524 were assessable for toxicity. In the population assessable for efficacy (n = 407), logistic regression analysis showed that increasing docetaxel dose was significantly associated with higher response rate (P = .007) and improved time to progression (TTP; P = .014). In the ITT analysis, a significant dose-response relationship was observed for tumor response (P = .026) but not for TTP (P = .067). The incidences of most hematologic and nonhematologic toxicities were related to increasing dose, with grade 3 to 4 neutropenia occurring in 76.4%, 83.7%, and 93.4% and febrile neutropenia occurring in 4.7%, 7.4%, and 14.1% of patients administered the 60, 75, and 100 mg/m 2 doses, respectively. One death was considered treatment related. Conclusion A relationship between increasing dose of docetaxel and increased tumor response was observed across the dose range of 60 to 100 mg/m 2 every 3 weeks. Toxicities were related to increasing dose. Depending on the therapy goal, any of the doses studied may be appropriate for second-line treatment of advanced breast cancer.