A Randomized Phase III Tial Of Paclitaxel Versus Paclitaxel Plus Bevacizumab (rhuMAb VEGF) As First-Line Therapy For Locally Recurrent or Metastatic Breast Cancer

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Histologically or cytologically confirmed adenocarcinoma of the breast

- Locally recurrent disease that is not amenable to surgical resection with curative
intent OR

- Metastatic disease

- No HER-2-overexpressing (3+) breast cancer unless previously treated with trastuzumab
(Herceptin)

- Unknown HER-2 status allowed provided herceptin-based therapy inappropriate or
not indicated

- No prior or radiologic evidence of CNS metastases, including previously treated,
resected, or asymptomatic brain lesions or leptomeningeal involvement by head CT scan
or MRI

- Hormone receptor status:

- Not specified

PATIENT CHARACTERISTICS:

Age:

- 18 and over

Sex:

- Male or female

Menopausal status:

- Not specified

Performance status:

- ECOG 0-1

Life expectancy:

- Not specified

Hematopoietic:

- Absolute neutrophil count at least 1,500/mm^3

- Platelet count at least 100,000/mm^3

- No prior bleeding diathesis

Hepatic:

- Bilirubin no greater than 1.5 mg/dL

- SGOT no greater than 2 times upper limit of normal (ULN) (5 times ULN for known liver
involvement)

- PT/PTT no greater than 1.5 times normal

- INR no greater than 1.5 times normal

Renal:

- Creatinine no greater than 2.0 mg/dL

- No proteinuria by dipstick urinalysis

- Trace proteinuria allowed

- Proteinuria less than 500 mg by 24-hour urine collection if proteinuria at least 1+
by urinalysis

Cardiovascular:

- No clinically significant cardiovascular disease

- No myocardial infarction within the past 12 months

- No unstable angina

- No prior deep vein thrombosis

- No grade 2 or greater peripheral vascular disease

- No uncontrolled congestive heart failure

- No uncontrolled hypertension (systolic blood pressure greater than 170 mmHg and
diastolic blood pressure greater than 95 mm Hg)

- No prior cerebrovascular accident

Pulmonary:

- No prior pulmonary embolism

Other:

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective non-hormonal contraception

- No history of seizures

- No non-healing wound or fracture

- No hypersensitivity to paclitaxel, Cremophor EL, Chinese hamster ovary cell products,
or other recombinant human antibodies

- No active infection requiring parenteral antibiotics

PRIOR CONCURRENT THERAPY:

Biologic therapy:

- See Disease Characteristics

Chemotherapy:

- No prior chemotherapy for locally recurrent or metastatic breast cancer

- At least 12 months since prior adjuvant or neoadjuvant taxane therapy

- At least 3 weeks since prior adjuvant chemotherapy

Endocrine therapy:

- At least 3 weeks since prior hormonal therapy for locally recurrent or metastatic
breast cancer

Radiotherapy:

- At least 3 weeks since prior radiotherapy

- No prior radiotherapy to only site of disease

- No concurrent local radiotherapy for pain control or life-threatening situations
(e.g, superior vena cava syndrome, spinal cord compression, or CNS metastases)

Surgery:

- At least 4 weeks since prior major surgical procedure except placement of vascular
access device or breast biopsy

- At least 7 days since prior minor surgical procedure, including placement of an
access device or fine needle aspiration

Other:

- At least 10 days since prior anticoagulant therapy (low-dose anticoagulant therapy to
maintain patency of a vascular access device allowed)

- At least 10 days since prior and no concurrent daily aspirin (more than 325 mg/day)
or other non-steroidal anti-inflammatory medication known to inhibit platelet
function

- No concurrent dipyridamole, ticlopidine, clopidogrel, or cilostazol