A phase II feasibility trial of dose-dense docetaxel followed by doxorubicin/cyclophosphamide as adjuvant or neoadjuvant treatment for women with node-positive or high-risk node-negative breast cancer

Purpose: Dose-dense adjuvant chemotherapy with doxorubicin/cyclophosphamide (AC) followed by paclitaxel has results compared with standard dosing at 3-week intervals. Because docetaxel might be more active than paclitaxel in the treatment of metastatic breast cancer, we explored the feasibility of substituting docetaxel for paclitaxel in dose-dense adjuvant therapy. Patients and Methods: Seventy-six patients with node-positive breast cancer received treatment with 4 cycles of docetaxel followed by 4 cycles of AC administered with pegfilgrastim at 2-week intervals. When treatment proved difficult for the first 33 patients, 2 additional cohorts were treated: first, with a reduction of pegfilgrastim and dexamethasone prophylaxis doses (cohort 2) and then with a reduction of docetaxel from 100 mg/m(2) to 75 mg/m(2) (cohort 3). Results: Treatment with dose-dense docetaxel at 100 mg/m2 resulted in unacceptable toxicity (24% of patients required hospitalization) and compromised subsequent dosing of AC as a result of neutropenia on the day of scheduled treatment. Only 21 patients (40%) who received docetaxel 100 mg/m(2) were able to receive all 8 doses at full dose and on schedule. Reduction of docetaxel to 75 mg/m(2) allowed 74% of patients to receive all 8 doses as scheduled. Delivery of AC as scheduled occurred in 82% of patients who received docetaxel 75 mg/m(2) versus 40% when docetaxel 100 mg/m(2) was administered. Conclusion: Full-dose docetaxel is difficult to administer as part of this dose-dense treatment regimen. Docetaxel 75 mg/m(2) can be administered with improved subsequent delivery of 4 courses of dose-dense AC. Until comparative clinical studies are available, docetaxel should not be substituted for paclitaxel in dose-dense adjuvant chemotherapy for patients with high-risk breast cancer.