BETHESDA, Maryland-Neoadjuvant docetaxel(Drug information on docetaxel) (Taxotere) followed by surgery, adjuvant doxorubicin(Drug information on doxorubicin) and cyclophosphamide(Drug information on cyclophosphamide) (Cytoxan, Neosar), and radiation therapy is an active regimen for patients with stage III breast cancer. Among 41 patients, clinical response rates after no more than four cycles of docetaxel were 64% in the breast only and 58% in the breast plus axilla. These results from a phase II study were reported by Sandra Swain, MD, of the National Cancer Institute, Bethesda, MD (ASCO abstract 143). Describing the context for these results, Dr. Swain noted, "We previously reported outcomes in 33 women with stage III breast cancer treated with docetaxel 100 mg/m2 q3wk x 4, followed by surgery, doxorubicin 60 mg/m2 plus cyclophosphamide 600 mg/m2 q3wk x 4, and radiation (Br Ca Res Treat 46:74, 1997). Patients with estrogenreceptor- positive tumors received tamoxifen(Drug information on tamoxifen). Here we describe updated response and survival results from this phase II study." "Emerging phase II data supported docetaxel's significant single-agent activity in patients with metastatic breast cancer, including previously untreated and anthracycline- refractory disease. Evaluating a cytotoxic agent in the neoadjuvant setting provides an opportunity for assessing its potential impact in locally advanced disease, as a prelude to further exploration within multiagent adjuvant chemotherapy. Thus, we designed a multicenter phase II trial of neoadjuvant docetaxel, followed by surgery, adjuvant doxorubicin and cyclophosphamide, and then radiation therapy for locally advanced breast cancer." Study Design Eligibility criteria include stage III adenocarcinoma of the breast; bidimensionally measurable lesion; no disease outside of the breast, except for the ipsilateral axillary nodes; Karnofsky performance status ≥ 60 and no prior chemotherapy, immunotherapy, or hormonal therapy for breast cancer. Of the 45 patients enrolled in the study, patients completing each phase of treatment per protocol were docetaxel (38 patients), surgery (31), doxorubicin and cyclophosphamide (23), and radiation therapy (23). The primary end point of the study was clinical response to docetaxel. The secondary end points were pathologic complete response to docetaxel, adverse events and toxicity, median time to progression, and disease-free and overall survival (1-year and 2-year rates). Four of the 45 patients enrolled in the study were found to be ineligible. Among the 41 eligible patients, 36 in the breast plus axilla group were evaluable for clinical response, and 29 were evaluable for pathologic response. In the breast only category, 39 patients were evaluable for clinical response. Survival Rates and Responses One-year overall survival was 95% (39 of 41 patients) for all patients, 100% for stage IIIA patients, and 91% for stage IIIB patients. In the breast only group, complete response was 18%, and partial response was 46%. Overall complete response was 8% in this group, and partial response was 43%. Pathologic findings for the 31 patients having surgery after doxorubicin x 4 weeks were pathologic complete response (breast plus axilla) of 10%, plus 6% with less than 5 mm of residual invasive cancer. Median follow-up for the 41 eligible patients was 5.6 years and 5-year disease-free survival was 80%. Neutropenia was the most common grade 3/4 toxicity. The incidence of febrile neutropenia was 27% during docetaxel therapy and 2% with doxorubicin and cyclophosphamide. Grade 3/4 nonhematologic toxicities that occurred in ≥ 5% of patients included asthenia and diarrhea. Results Summarized In summarizing the results of the study, Dr. Swain said, "Among the 41 patients, clinical response rates after no more than four cycles of docetaxel were 64% in breast only and 58% in breast plus axilla. Based on this finding, we conclude that neoadjuvant docetaxel followed by surgery, adjuvant doxorubicin and cyclophosphamide, and radiation is an active regimen for patients with stage III breast cancer, with a pathologic complete response rate of 10% (breast plus axilla) and pN0 and pT0 rates of 38% and 14%, respectively. "This is consistent with the data from National Surgical Adjuvant Breast and Bowel Project (NSABP) B-27, in which lower stage patients were treated. In that trial, the pathologic complete response rate (breast only) was 13.7% for neoadjuvant doxorubicin and cyclophosphamide, and increased to 25.6% with the addition of docetaxel after doxorubicin and cyclophosphamide- an absolute increase of about 12%. This finding suggests that docetaxel as a single agent makes a significant contribution to response." In concluding, Dr. Swain observed, "The 5-year overall survival rate of 80% for patients with stage III breast cancer is very encouraging, as are the 5-year overall survival rates for the subgroups of patients with stage IIIA (84%) and IIIB (77%) disease. The findings indicate that neoadjuvant docetaxel followed by surgery, adjuvant doxorubicin, and cyclophosphamide, and radiation therapy is an active regimen for patients with stage III breast cancer."