Metronomic Therapy in Metastatic Breast Cancer.

Inclusion criteria

DISEASE CHARACTERISTICS: * Histologically or cytologically confirmed adenocarcinoma of the breast * Locally advanced, recurrent, or metastatic disease * HER2-negative disease * Measurable or evaluable disease * Candidate for taxane-based chemotherapy * No presence or history of CNS metastasis * Clinical suspicion of CNS metastasis must be confirmed by CT or MRI scan * Hormone receptor status not specified PATIENT CHARACTERISTICS: * Menopausal status not specified * WHO performance status 0-2 * Neutrophil count ≥ 1.5 x 10\^9/L * Platelet count ≥ 100 x 10\^9/L * Hemoglobin ≥ 80 g/L * Bilirubin ≤ 1.5 times upper limit of normal (ULN) * AST ≤ 5 times ULN * Alkaline phosphatase ≤ 2.5 times ULN (≤ 5 times ULN in case of liver metastases or ≤ 10 times ULN in case of bone metastases) * Serum creatinine ≤ 1.5 times ULN * Urine protein \< 2+ by dipstick OR ≤ 1 g by 24-hour urine collection * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception during and for 12 months after completion of study therapy * Patients with INR \> 1.5 (or Quick ≤ 70%) OR aPTT \> 1.5 times ULN within 7 days prior to expected first trial treatment must be receiving anticoagulant medication * Patients receiving full-dose oral or parental anticoagulants may be included in the trial provided anticoagulant dosing has been stable for at least 2 weeks prior to trial entry and the appropriate coagulation monitoring tests are within local therapeutic limits * Must be compliant and geographically proximal for staging and follow-up * No previous malignancy within the past 5 years except for adequately treated carcinoma in situ of the cervix or localized nonmelanoma skin cancer * No known hypersensitivity to trial drugs or its active compound (e.g., fluoropyrimidine), any other components of the trial drugs, or drugs formulated with cremophor EL including hypersensitivity to Chinese hamster ovary cell products or any other humanized recombinant antibodies * No preexisting peripheral motor or sensory neuropathy \> NCI CTCAE grade 2 (i.e., moderate symptoms or limiting instrumental activities of daily living) * No history or evidence of inherited bleeding diathesis, coagulopathy with the risk of bleeding, serious nonhealing wound, active peptic ulcer, nonhealing bone fracture, or bleeding metastases * No history of abdominal fistula, grade 4 bowel obstruction, or gastrointestinal perforation or intra-abdominal abscess within the past 6 months * No evidence of other medical conditions that would impair the ability of the patient to participate in the trial or might preclude therapy with trial drugs, including any of the following: * DPD deficiency * Severe respiratory, cardiac, hepatic, or renal disease * Active infection * Uncontrolled diabetes mellitus * Uncontrolled hypertension ≥ 140/100 mm Hg * Myocardial infarction within the past 12 months * Cerebrovascular accident or stroke within the past 6 months * History of hemorrhagic disorders * No psychiatric disorder precluding understanding of information on trial-related topics, giving informed consent, filling out quality-of-life forms, or interfering with compliance for oral drug intake PRIOR CONCURRENT THERAPY: * No prior chemotherapy for metastatic or locally recurrent breast cancer * No prior radiotherapy for metastatic disease * Prior radiotherapy for the relief of metastatic bone pain allowed provided no more than 30% of marrow-bearing bone was irradiated * At least 12 months since prior bevacizumab or other anti-VEGF therapy * At least 12 months since prior capecitabine, continuous (\> 24 hours) fluorouracil infusion, or other oral fluoropyrimidine (e.g., eniluracil/fluorouracil, uracil/tegafur, S1, or emitefur) * At least 12 months since prior taxane-based chemotherapy * At least 6 months since other prior (neo)adjuvant chemotherapy * At least 30 days since prior treatment in another clinical trial * At least 24 hours since prior minor surgical procedures * At least 28 days since prior and no concurrent major surgical procedures (including open biopsy) and no anticipation of the need for major surgery during the first course of this trial * At least 10 days since prior hormone therapy for metastatic disease * No continuous daily treatment with corticosteroid except for inhaled steroids * No concurrent chronic daily aspirin \> 325 mg/day * No concurrent chronic daily clopidogrel \> 75 mg/day * No other concurrent anticancer treatments * No other concurrent investigational treatments or experimental drugs * No other concurrent drug therapy contraindicated for use with the trial drugs