docetaxel, doxorubicin (a), cyclophosphamide (c) (tac) vs 5-fluorouracil, a, c (5fac) breast cancer adjuvant treatment

Conditions: Breast Neoplasms

Summary: 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).

Eligibility criteria:
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.

Keywords: high risk node negative breast cancer disease-free survival quality of life