Inclusion Criteria:
- Unilateral or bilateral primary carcinoma of the breast,
- Tumor lesion in the breast with a palpable size of >= 2 cm. The lesion has to be measurable in two-dimensions preferably by sonography. In case of inflammatory disease the extent of inflammation can be used as measurable lesion;
- Patients should have stages of disease in which adjuvant chemotherapy would be considered.
- Women of childbearing potential must have a negative serum pregnancy test
- Negative HER-2/neu status
- Karnofsky Performance status index >= 80%;
- Normal cardiac function
- Laboratory requirements:
Absolute neutrophile count (ANC) >= 2,0 x 109/L and Platelets >= 100 x 109/L and Hemoglobin >= 10 g/dL (>= 6.2 mmol/L) INR ≤ 1.5 ULN and PTT ≤ 1.5 ULN within 14 days prior to enrolment ASAT or ALAT < 2.5 x ULN Alkaline phosphatase ≤ 5 UNL. Patients with ASAT and/or ALAT > 1,5 x UNL associated with alkaline phosphatase > 2,5 x UNL are not eligible for the study Total bilirubin < 1 X UNL Creatinine ≤ 175 µmol/L (2 mg/dl). The calculated creatinine clearance should be ≥ 60 mL/min.
Paraffin tumor tissue block and each one serum and one plasma sample centrally made available
- Complete staging work-up within 3 months prior to registration.
- Patients must be available and compliant for treatment and follow-up. Patients registered on this trial must be treated and followed up at the participating or a cooperating center.
Exclusion Criteria:
- Patients with low or moderate risk, which are only doubtful candidates for adjuvant chemotherapy and do not fulfil the inclusion criteria No. 5.
- Evidence of distant metastasis;
- Prior chemotherapy for any malignancy;
- Prior radiation therapy for breast cancer;
- Preexisting rhagades at hand and feet and other skin problems (e.g. psoriasis)
- Pregnant or lactating patients.
- Pre-existing motor or sensory neuropathy of a severity >= grade 2 by NCI criteria; 7. Concurrent treatment with: Chronic corticosteroids unless initiated > 6 months prior to study entry and at low dose (< 20 mg methylprednisolone or equivalent); Sex hormones. Prior treatment must be stopped before study entry; Patients with increased risk of bleeding due to concurrent therapeutic or prophylactic anticoagulative treatment. Low dose of coumarines are permitted.
Other experimental drugs or any other anti-cancer therapy; Drugs recognized as being strong inhibitors or inducers of the isoenzyme CYP3A within the last 5 days or their expected need 8. Other serious illness or medical condition:
- Previous malignant disease without being disease-free of less than 5 years (except CIS of the Cervix and non-melanomatous skin cancer)
- Known or suspected congestive heart failure (≥NYHA II) and/or coronary heart disease, angina pectoris requiring antianginal medication, previous history of myocardial infarction, evidence of transmural infarction on ECG, un- or poorly controlled arterial hypertension, rhythm abnormalities requiring permanent treatment, clinically significant valvular heart disease
- Thrombotic or embolic events
- Hemorrhage/bleeding event ≥ Grade 3 within 4 weeks prior study entry
- Evidence or history of bleeding diathesis or coagulopathy
- History of significant neurological or psychiatric disorders
- Patients with seizure disorders requiring medication such as steroids or antiepileptics
- Currently active infection
- History of HIV infection or chronic hepatitis B or C
- Serious non healing wound, ulcer or bone fracture
- Patients with prior immunosuppressive treatment
- Severe pulmonary condition/illness
- Disease significantly affecting gastrointestinal function,
- Patients with severe liver disease
- Major surgery, open biopsy or significant traumatic injury within 4 weeks of first dose of study drug
- Definite contraindications for the use of corticosteroids
- Inadequate general condition (not fit for anthracycline/taxane-containing chemotherapy)