Docetaxel, Doxorubicin (A), Cyclophosphamide (C) (TAC) vs 5-Fluorouracil, A, C (5FAC) Breast Cancer Adjuvant Treatment
Docetaxel, Doxorubicin (A), Cyclophosphamide (C) (TAC) vs 5-Fluorouracil, A, C (5FAC) Breast Cancer Adjuvant Treatment
This is a prospective, non-blinded randomized phase III trial. Patients will be
 post-surgically stratified at inclusion first according to the participating institution,
 then according to menopausal status and will be randomly assigned to receive either:

 -  TAC: Docetaxel 75 mg/m2 as a 1 hour intravenous (i.v.) infusion on day 1 every 3 weeks
 (q3w) in combination with doxorubicin 50 mg/m2 as an i.v. bolus and cyclophosphamide 500
 mg/m2 as an i.v. bolus on day 1 every 3 weeks.

 -  FAC: 5-fluorouracil 500 mg/m2 as an i.v. bolus on day 1 every 3 weeks in combination
 with doxorubicin 50 mg/m2 as an i.v. bolus and cyclophosphamide 500 mg/m2 as an i.v.
 bolus on day 1 every 3 weeks.
Primary objective:

 -  To compare disease-free survival (DFS) after treatment with docetaxel in combination
 with doxorubicin and cyclophosphamide (TAC) to 5-Fluorouracil in combination with
 doxorubicin and cyclophosphamide (FAC) as adjuvant treatment of high risk operable
 breast cancer patients with negative axillary lymph nodes.

 Secondary objectives:

 -  To compare overall survival (OS) between the 2 above mentioned arms.

 -  To compare toxicity and quality of life between the 2 above mentioned arms.

 -  To evaluate pathologic markers for predicting efficacy (hormonal receptors and human
 epidermal growth factor receptor 2 (HER2) protein expression).
Inclusion Criteria:

 -  Written informed consent

 -  Operable breast cancer patients (T1-T3) with negative axillary lymph nodes (10
 axillary nodes dissection) and high risk criteria according to St. Gallen consensus
 criteria.

 -  Histologically proven breast cancer. Interval between surgery and registration is less
 than 60 days.

 -  Definitive surgical treatment must be either mastectomy, or breast conservative
 surgery. Margins of resected specimen from surgery must be histologically free of
 invasive adenocarcinoma and ductal carcinoma in-situ (DCIS). Lobular carcinoma in-situ
 is not considered as positive margin.

 -  Patients without proven metastatic disease.

 -  Estrogen and progesterone receptors performed on the primary tumour prior to
 randomization.

 -  Age between 18 years and 70 years.

 -  Karnofsky performance status index > 80 %.

 -  Adequate hepatic, renal and heart functions.

 -  Adequate hematology levels.

 -  Negative pregnancy test

 Exclusion Criteria:

 -  Prior systemic anticancer therapy for breast cancer (immunotherapy, hormonotherapy,
 chemotherapy).

 -  Prior anthracycline therapy or taxoids (paclitaxel, docetaxel) for any malignancy.

 -  Prior radiation therapy for breast cancer.

 -  Bilateral invasive breast cancer.

 -  Pregnant, or lactating patients.

 -  Patients of childbearing potential must implement adequate non-hormonal contraceptive
 measures during study treatment .

 -  Any T4 or N1-3 or M1 breast cancer.

 -  Pre-existing motor or sensory neurotoxicity of a severity grade 2 by NCI criteria.

 -  Other serious illness or medical condition

 -  Past or current history of neoplasm other than breast carcinoma.

 -  Ipsilateral ductal carcinoma in-situ (DCIS) of the breast.

 -  Lobular carcinoma in-situ (LCIS) of the breast.

 -  Chronic treatment with corticosteroids unless initiated > 6 months prior to study
 entry and at low dose

 -  Concurrent treatment with ovarian hormonal replacement therapy. Prior treatment should
 be stopped before study entry.

 -  Definite contraindications for the use of corticosteroids.

 -  Concurrent treatment with other experimental drugs.

 -  Participation in another clinical trial with any investigational not marketed drug
 within 30 days prior to study entry.

 -  Concurrent treatment with any other anti-cancer therapy.

 -  Male patients.