Capecitabine, Vinorelbine, and Trastuzumab in Treating Patients With Metastatic Breast Cancer

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed invasive breast cancer

  • Metastatic disease

• HER2/neu-positive by immunohistochemistry (3+ by HercepTest^™ or equivalent) OR positive for amplification by fluorescent in situ hybridization

  • Testing may be performed in the primary tumor or the metastatic site
• Received prior anthracycline or taxane as adjuvant therapy or for metastatic disease

• Measurable disease

  • At least one measurable lesion ≥ 2.0 cm by CT scan or MRI OR ≥ 1.0 cm by spiral CT scan

  • The following are considered non-measurable disease:

    • Bone lesions
    • Leptomeningeal disease
    • Ascites
    • Pleural/pericardial effusion
    • Inflammatory breast disease
    • Lymphangitis cutis/pulmonis
    • Abdominal masses that are not confirmed and followed by imaging techniques
    • Cystic lesions
• No bone metastases as the only evidence of metastasis
• Previously treated CNS metastases allowed provided disease has been stable for ≥ the past 3 months

• Hormone receptor status:

  • Not specified

PATIENT CHARACTERISTICS:

Age

• 18 and over

Sex

• Female or male

Menopausal status

• Not specified

Performance status

• ECOG 0-2

Life expectancy

• At least 12 weeks

Hematopoietic

• Absolute neutrophil count ≥ 1,500/mm^3
• Hemoglobin ≥ 8.0 g/dL
• Platelet count ≥ 100,000/mm^3
• No known uncontrolled coagulopathy

Hepatic

• Bilirubin ≤ 3.0 times the upper limit of normal (ULN)

• One of the following must be true:

  • AST or ALT ≤ 5 times ULN AND alkaline phosphatase normal
  • Alkaline phosphatase ≤ 5 times ULN AND AST or ALT normal
  • Alkaline phosphatase ≤ 2.5 times ULN AND AST or ALT ≤ 1.5 times ULN
• INR ≤ 1.5 times ULN

Renal

• Calcium ≤ 11.5 mg/dL
• Creatinine ≤ 1.5 times ULN
• Creatinine clearance ≥ 30 mL/min

Cardiovascular

• LVEF ≥ 50% by MUGA or echocardiogram
• No clinically significant (i.e., active) cardiac disease
• No congestive heart failure
• No symptomatic coronary artery disease
• No myocardial infarction within the past 12 months
• No cardiac arrhythmia not controlled with medication

Gastrointestinal

• Able to take oral medication
• No lack of physical integrity of the upper gastrointestinal tract
• No clinically significant malabsorption syndrome

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 30 days after study participation
• No history of allergy or hypersensitivity to study drugs, drug product excipients, including polysorbate 80, or chemically similar agents
• No prior unanticipated severe reaction to fluoropyrimidine therapy
• No know hypersensitivity to fluorouracil
• No known dihydropyrimidine dehydrogenase deficiency
• No history of uncontrolled seizures or CNS disorders
• No clinically significant psychiatric disability that would preclude giving informed consent or study compliance
• No other serious uncontrolled infection or disease
• No other malignancy within the past 5 years except cured basal cell skin cancer, carcinoma in situ of the cervix, or contralateral breast cancer

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Prior adjuvant trastuzumab (Herceptin^®) allowed as adjuvant or first-line therapy for metastatic disease
• No concurrent immunotherapy

Chemotherapy

• See Disease Characteristics
• No more than 1 prior chemotherapy regimen in the advanced or metastatic (non-adjuvant) setting
• No prior continuous (≥ 24 hours) fluorouracil infusion
• No prior capecitabine
• No prior oral fluoropyrimidines (e.g., eniluracil and fluorouracil, uracil and tegafur, S1, or emitefur)

Endocrine therapy

• At least 1 day since prior hormonal therapy
• No concurrent hormonal therapy

Radiotherapy

• More than 4 weeks since prior radiotherapy to the axial skeleton (i.e., skull, spinal column, sternum, or ribs)
• No concurrent radiotherapy

Surgery

• More than 4 weeks since prior major surgery
• No prior organ allografts requiring immunosuppressive therapy

Other

• More than 4 weeks since prior investigational drugs
• No concurrent sorivudine or its chemically related analogues (e.g., brivudine)
• No concurrent allopurinol, metronidazole, or cimetidine
• No other concurrent cytotoxic agents
• No other concurrent investigational drugs
• No other concurrent anticancer therapy