Docetaxel/Epirubicin/Bevacizumab as First Line Therapy for Metastatic HER2 Negative Breast Cancer

Docetaxel-epirubicin Plus Bevacizumab as First Line Therapy for Patients With Metastatic and HER2 Negative Breast Cancer. A Multicenter Phase I-II Study

This study will evaluate the efficacy and toxicity of docetaxel-epirubicin combination plus bevacizumab as first line treatment in patients with metastatic and HER2 negative breast cancer.

A phase II trial with 142 patients demonstrated that therapy with docetaxel plus epirubicin is highly active first-line therapy for metastatic breast cancer, with acceptable toxicity profile. Recently initial therapy of metastatic breast cancer with paclitaxel plus bevacizumab demonstrated prolonged progression-free survival, as compared with paclitaxel alone. This study will evaluate the efficacy and toxicity of docetaxel-epirubicin combination plus bevacizumab as first line treatment in patients with metastatic and HER2 negative breast cancer. Furthermore, the efficacy of the combination therapy will be correlated with the presence of circulating tumor cells (CTCs) in this population.

Inclusion Criteria:

• Histologically- or cytologically- confirmed metastatic breast adenocarcinoma
• No HER2 overexpression or gene amplification
• No previous therapy for metastatic breast cancer is allowed
• Age 18-75 years
• At least 12 months interval since prior adjuvant therapy with taxanes and/or anthracyclines
• Measurable disease as defined by the presence of at least one measurable lesion (except bone metastases, ascites or pleural effusions)
• Performance status (WHO) 0-2
• Adequate liver (serum bilirubin <1.5 times the upper normal limit, AST and ALT <2.5 times the upper normal limit in the absence of demonstrable liver metastases, or <5 times the UNL in the presence of liver metastases)
• Adequate renal function (serum creatinine <1.5 times the upper normal limit
• Adequate bone marrow function (neutrophils ≥ 1.5x 109 /L, and platelets ≥ 100x 109 /L)
• Written informed consent

Exclusion Criteria:

• Active infection
• Brain metastases
• History of significant cardiac disease (unstable angina, congestive heart failure, myocardial infarction within the previous 6 months, ventricular arrhythmias)
• History of stroke
• Anticoagulation therapy (except of low dose aspirin <325mg)
• Other invasive malignancy except nonmelanoma skin cancer
• Psychiatric illness or social situation that would preclude study compliance
• Pregnant or lactating women