Docetaxel, Doxorubicin (A), Cyclophosphamide (C) (TAC) vs 5-Fluorouracil, A, C (5FAC) Breast Cancer Adjuvant Treatment

Phase III Randomized Comparing Docetaxel, Doxorubicin and Cyclophosphamide (TAC) vs 5-Fluorouracil, Doxorubicin and Cyclophosphamide (FAC) as Adjuvant Treatment of High Risk Operable Breast Cancer Patients With Negative Axillary Lymph Nodes

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.