Randomised Comparison of Adjuvant Docetaxel / Cyclophosphamide With Sequential Adjuvant EC / Docetaxel Chemotherapy in Patients With HER2/Neu Negative Early Breast Cancer
Inclusion Criteria
Inclusion Criteria(Screening):
- Female patients, age at diagnosis 18 - 75 years
- Histological confirmed unilateral primary invasive carcinoma of the breast
- Adequate surgical treatment with complete resection of the tumor (R0) and resection
of > or = 10 axillary nodes or SLN in clinically N0 patients
- T1 - T4 (if operable, inflammatory breast cancer is excluded)
- Her-2 non-over expressing tumor confirmed by IHC/FISH
- Estrogen and/or progesterone receptor analysis performed on the primary tumor prior
to randomization. Results must be known at the time of randomization
- Node positive disease or node negative disease with at least one other risk factor
(tumor size > or = 2 cm, grade > or = 2, ER and PR negative, high uPA//PAI-1 levels)
- No evidence for distant metastasis (M0) after conventional staging
- Performance Status ECOG < or = 1 or KI > or = 80 %
- The patient must be accessible for treatment and follow-up
- Written informed consent for central pathology review and evaluation of Recurrence
Score (HR positive) and participation in the planB trial prior to beginning specific
protocol procedures
HR positive patients:
- Patient willingness to participate in adjuvant chemotherapy planB trial if RS > 11
- Indication for chemotherapy given provided either > 4 involved lymph nodes or RS > 11
in 1-3 lymph nodes or N0 disease
Additional Inclusion Criteria (Randomisation to chemotherapy):
- Laboratory requirements (within 21 days prior to randomization):
- Leucocytes > or = 3.5 109/L
- platelets > or = 100 109/L
- haemoglobin > or = 10 g/dL
- total bilirubin < or = 1 ULN
- ASAT (SGOT) and ALAT (SGPT) < or = 2.5 UNL
- creatinine < 175 ymol/L (2 mg/dL)
- Negative pregnancy test (urine or serum) within 7 days prior to randomization in
premenopausal patients
- LVEF within normal limits of each institution measured by echocardiography or MUGA
scan and
Exclusion Criteria(Screening):
- HER2 over expression confirmed by IHC/FISH/CISH
- Known hypersensitivity reaction to the compounds or incorporated substances
- Known polyneuropathy > or = grade 2
- Severe and relevant comorbidity that would interact with the application of cytotoxic
agents or the participation in the study including acute cystitis and ischuria and
chronic kidney disease.
- Prior malignancy with a disease-free survival of < 10 years, except curatively
treated basalioma of the skin, pTis of the cervix uteri or ipsilateral ductal
carcinoma in-situ (DCISpTis of the breast)
- Non-operable breast cancer including inflammatory breast cancer
- Previous or concurrent treatment with cytotoxic agents for any reason after
consultation with the sponsor
- Concurrent treatment with other experimental drugs. Participation in another clinical
trial with any investigational not marketed drug within 30 days prior to study entry
- Male breast cancer
- Concurrent pregnancy; patients of childbearing potential must implement a highly
effective (less then 1% failure rate) non-hormonal contraceptive measures during the
study treatment
- Breast feeding woman
- Sequential breast cancer
- Lack of patient compliance
Additional Exclusion Criteria (Randomisation):
- Inadequate organ function including:
- Leucocytes < 3,5 G/l
- platelets < 100 G/l
- creatinine or bilirubin above normal limits
- alkaline phosphatise > 5 UNL
- ASAT and/or ALAT associated with AP > 2.5 UNL
- uncompensated cardiac function
- Time since axillary dissection > 42 days