Bevacizumab and Doxorubicin Hydrochloride Liposome in Treating Women With Locally Recurrent or Metastatic Breast Cancer

DISEASE CHARACTERISTICS:

* Cytologically or histologically confirmed breast cancer

  * Metastatic OR locally recurrent disease
  * Unresectable disease
  * Not amenable to radiotherapy
* Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR ≥ 10 mm by spiral CT scan

  * Measurable disease must be outside irradiated areas
* ErbB2-negative disease by immunohistochemistry (negative or 1+) or fluorescent in situ hybridization (FISH)
* No known CNS metastases, even if previously treated
* Hormone receptor status not specified

PATIENT CHARACTERISTICS:

* Female
* Menopausal status not specified
* WHO performance status 0-1
* LVEF ≥ 55%
* Hemoglobin ≥ 10.0 g/dL
* Absolute neutrophil count ≥ 1,500/mm³
* Platelet count ≥ 100,000/mm³
* Bilirubin \< 2 times upper limit of normal (ULN)
* ALT ≤ 2.5 times ULN (5 times ULN if liver metastases are present)
* Alkaline phosphatase (AP) ≤ 2.5 times ULN

  * AP \> 2.5 times ULN and ≤ 6 times ULN allowed if ALT ≤ 1.5 times ULN
  * AP \> 6 times ULN allowed if ALT normal
* Creatinine ≤ 1.5 times ULN
* Proteinuria \< 2+ by dipstick OR protein ≤ 1 g/24hr-urine collection
* INR ≤ 1.5 OR Quick ≥ 70%
* aPTT ≤ 1.5 times ULN
* No peripheral neuropathy \> grade 2
* No history or evidence of hereditary bleeding diathesis or coagulopathy with the risk of bleeding
* No uncontrolled hypertension, defined as systolic blood pressure (BP) \> 150 mm Hg and/or diastolic BP \> 100 mm Hg, measured repeatedly at \> 2 visits despite adequate treatment with ≥ 2 different antihypertensive drugs
* No clinically significant cardiovascular disease, including the following:

  * Cerebrovascular accident or stroke within the past 6 months
  * Myocardial infarction within the past 6 months
  * Unstable angina
  * New York Heart Association class II-IV congestive heart failure
  * Serious cardiac arrhythmia (e.g., ventricular arrhythmia, high-grade atrioventricular-block) not controlled by medication or requiring medication which might interfere with regularity of the study treatment
* No serious nonhealing wound, active peptic ulcer, nonhealing bone fracture, or bleeding skin metastases
* No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 6 months
* No active infection requiring IV antibiotics
* No known hypersensitivity to any of the study drugs or excipients
* No known hypersensitivity to Chinese hamster ovary cell products or other recombinant human or humanized antibodies
* No evidence of any other disease that contraindicates the use of an investigational drug, that may affect patient compliance with study routines, or places the patient at high risk for treatment-related complications including, but not limited to, the following:

  * Metabolic dysfunction
  * Physical examination finding
  * Psychological dysfunction
  * Clinical laboratory finding giving reasonable suspicion of a disease or condition
* No known CNS disease unrelated to cancer (e.g., uncontrolled seizures), unless adequately treated with standard medical therapy
* No high-risk factors for bleeding, including the following:

  * Coagulation parameters outside range
  * Need for concurrent anticoagulant therapy
  * Insufficient time gap after surgical procedures
* No other malignancy within the past 5 years except for adequately treated basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix
* No significant traumatic injury within the past 28 days
* No known HIV positivity
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception during and for 12 months after completion of study therapy

PRIOR CONCURRENT THERAPY:

* No prior chemotherapy for metastatic or inoperable locally recurrent breast cancer
* No prior bevacizumab or other anti-vascular endothelial growth factor drug therapy
* No prior radiotherapy involving the heart (usual irradiation dose to breast or chest wall allowed)
* More than 12 months since prior neoadjuvant or adjuvant chemotherapy
* No neoadjuvant or adjuvant doxorubicin hydrochloride with cumulative dose \> 360 mg/m² or epirubicin hydrochloride with cumulative dose \> 720 mg/m²
* More than 6 months since prior adjuvant radiotherapy
* More than 28 days since prior major surgical procedure with high risk of bleeding
* More than 24 hours since prior minor surgical procedures
* More than 10 days since prior acetylsalicylic acid (\> 325 mg/day) or clopidogrel bisulfate (\> 75 mg/day)
* More than 10 days since prior and no concurrent use of full-dose oral or parenteral anticoagulants or thrombolytic agents for therapeutic purposes

  * Prophylactic use of anticoagulants allowed (e.g., for maintenance of venous catheter)
* More than 30 days since prior investigational therapies or participation in other investigational studies
* No concurrent hormonal therapy
* No other concurrent antineoplastic or antitumor therapy
* No other concurrent investigational drugs
* No concurrent radiotherapy
* No concurrent nonsteroidal anti-inflammatory drugs with activity on platelets and gastric mucosa (e.g., dipyridamole, clopidogrel bisulfate, acetylsalicylic acid)
* No anticipated need for major surgery during the course of the study treatment