Docetaxel, Gemcitabine and Bevacizumab for Metastatic Breast Cancer

Docetaxel plus gemcitabine is an active combination in the salvage treatment for metastatic breast cancer. Administered every two weeks, this combination has a favorable toxicity profile, and promising activity in > 1st line treatment for metastatic breast cancer. 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 addition of bevacizumab to a biweekly regimen of docetaxel and gemcitabine in the salvage therapy for metastatic breast cancer.

Inclusion criteria

• Histologically- or cytologically- confirmed metastatic breast adenocarcinoma
• No HER2 overexpression or gene amplification
• At least one previous chemotherapy regimen for metastatic breast cancer
• Age ≥18 years
• Performance status (WHO) 0-2
• Life expectancy of at least 12 weeks
• Measurable disease as defined by at least 1 bidimensionally measurable lesion ≥ 20 X 10 mm
• Performance status (WHO) 0-2
• Adequate liver function (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 upper normal limit in the presence of liver metastases), adequate renal function (serum creatinine <1.5 times the upper normal limit) and bone marrow ≥ 1,500/mm3, PLT ≥ 100,000/mm3, Hgb ≥ 9 g/dL) function
• Written informed consent

Exclusion criteria

• Pregnant or lactating women
• Progressive brain metastases according to clinical or radiological criteria
• Brain metastases without prior radiation therapy
• Radiation therapy within the previous 4 weeks
• Previous radiation therapy to the only measurable lesion
• Proteinuria ≥ 500 mgr of protein daily
• Uncontrolled hypertension
• Documented hemorrhagic diathesis or coagulation disorder
• Cardiovascular disease (class II-IV NYHA congestive heart failure, myocardial infarction within the previous 4 months, unstable angina, LVEF < normal, ventricular arrhythmia, uncontrolled hypertension)
• Thrombotic event within the previous 6 months
• Concurrent use of aspirin > 325 mgr daily, low molecular weight heparin in therapeutic dose, warfarin or acenocoumarol, non-steroid anti-inflammatory agents
• Major surgical procedure within the previous 4 weeks
• Presence of nonhealing wound or fracture
• Peripheral neuropathy > grade 2 according to the NCI CTCAE (version 3.0)
• Any sustained chronic toxicity > grade 2 according to the NCI CTCAE (version 3.0)
• Uncontrolled infection
• Any serious, uncontrolled comorbidity on the investigator's judgment
• Other cancer within the previous 5 years, except non-melanoma skin cancer and in situ cervical cancer
• Serious psychiatric illness