Purpose: To evaluate the safety and efficacy of bevacizumab and weekly docetaxel as first- or second-line therapy in patients with metastatic breast cancer (MBC). Patients and Methods: Twenty-seven MBC patients received i.v. bevacizumab at 10 mg/kg on days 1 and 15 in combination with i.v. docetaxel 35 mg/m2 on days 1, 8, and 15 of a 28-day cycle. Primary end points were to assess toxicity, overall response rate, and progression-free survival. A secondary end point was to assess the relationship between plasma endothelial and cell adhesion markers and clinical outcomes. Results: One-hundred fifty-eight treatment cycles were administered with a median of six cycles (range 1-15 cycles) per patient. The most common grade 4 toxicities per patient were as follows: 2 (7%)—pulmonary embolus, 1 (4%)—febrile neutropenia, and 1 (4%)—infection; grade 3 toxicities were 4 (15%)—neutropenia, 4 (15%)—fatigue, 2 (7%)—neuropathy, 2 (7%)—athralgias, 2 (7%)—stomatitis, 1 (7%)—pleural effusion, and 1 (4%)—hypertension. The overall response rate was 52% [95% confidence interval (95% CI), 32-71%], median response duration was 6.0 months (95% CI, 4.6-6.5 months), and the median progression-free survival was 7.5 months (95% CI, 6.2-8.3 months). In hypothesis-generating univariate and limited multivariate analyses, E-selectin was statistically significantly associated with response to the combination. Conclusion: Bevazicumab in combination with weekly docetaxel is active with acceptable toxicities in MBC. Additional studies evaluating E-selectin as a marker of response to bevacizumab-containing chemotherapy are warranted.

Purpose. In most neoadjuvant chemotherapy regimens, the taxane is administered either in combination with an anthracycline or after an anthracycline-containing regimen. We sought to test the feasibility, safety, and determine the pathological complete response (pCR) rate of administering docetaxel first followed by epirubicin as neoadjuvant chemotherapy in women with clinical stage II, III breast cancer. Patients and Methods. Twenty-five women with newly diagnosed clinical stage IIB (n = 10), IIIA (n = 5), or IIIB (n = 10) received 3 cycles of docetaxel 100 mg/M2 intravenously (IV) every 3 weeks followed by 3 cycles of epirubicin 100 mg/M2 IV every 3 weeks. pCR was defined as the absence of invasive cancer in the breast at definitive surgery. Results. The median primary tumor size was 6 cm (range 1–12 cm), and 13 (52%) women had clinically palpable axillary lymph nodes. Patients received 149 of the 150 planned cycles of docetaxel and epirubicin without treatment delays, and only 3 (12%) patients had a dose reduction of docetaxel. Seven (28%) patients experienced febrile neutropenia, and 9 (36%) patients had grade 3 non-hematological toxicities with diarrhea being the most frequent in 3 (12%) patients. Six (24%) patients had pCR in the breast. Analysis of pre- and post-docetaxel biopsies from a subset of patients documented taxane-induced activation of mitogen-activated and stress-activated protein kinase pathways. Conclusion. Neoadjuvant docetaxel followed by epirubicin is well tolerated and active in breast cancer. To our knowledge, this is first description of docetaxel-induced activation of mitogen-activated and stress-activated protein kinase pathways in human breast cancer.