Bevacizumab in Combination with Metronomic Chemotherapy in Patients with Anthracycline- and Taxane-Refractory Breast Cancer

Abstract

A vascular endothelial growth factor (VEGF) inhibitor might enhance metronomic chemotherapy in previously treated metastatic breast cancer (MBC) patients. Anthra-cycline and taxane refractory MBC patients were given cyclophosphamide 50 mg p.o. daily, methotrexate 1 mg/kg i.v. every 14 days, and bevacizumab 10 mg/kg i.v. every 14 days. Trastuzumab was added in HER2-overexpressing tumors. 24 patients were enrolled and 22 were evaluable. All tumors had histologic grade II-III and most patients had ≥2 metastatic sites. After a median follow-up of 7.7 months the response rates were: complete response (CR) 0%, partial response (PR) 31.8% (95% CI 13.9-54.9%), stable disease for ≥24 weeks (SD) 31.8% (95% CI 13.9-54.9%). Clinical benefit (CB= CR + PR + SD>24w) 63.6% (95% CI 40.7-82.8%). Median progression-free survival (PFS) was 7.5 months; overall survival (OS) was 13.6 months. HER2-overex-pressing or high proliferative-index tumors had better 6-month PFS (75% vs. 34% in HER-negative tumors P= 0.043; 67% vs. 0% in Ki-67 ≥20% tumors, P = 0.015). Adverse effects were mild. The combination of bevacizumab and a metronomic-based chemotherapy was effective, well tolerated and provided clinical benefit in heavily-treated MBC patients.