Breast cancer
Current interventions as of 29/04/2013: Randomization to one of the treatment arms (6 cycles TAC or AC dd) ACdd: doxorubicin 60 mg/m2 i.v. bolus and cyclophosphamide 600 mg/m2 i.v. bolus on day 1 every 2 weeks. TAC: Doxorubicin 50 mg/m² as an i.v. bolus on day 1, followed by cyclophosphamide 500 mg/m2 as i.v. bolus and, after 1 hour, docetaxel 75 mg/m² as 1 hour i.v. infusion on day 1 every 3 weeks. Both Arms: - prophylactic pegfilgrastim 6 mg s.c. given 1 day after completion of administration of each chemotherapy cycle; - Radiotherapy, if indicated; - Endocrine treatment for at least 5 years, (according to the most recent Dutch national guidelines)starting 1 to 6 weeks after radiotherapy or 3 to 6 weeks after chemotherapy for patients with positive estrogen and/or progesterone receptors. HER2 positive patients For HER2 positive patients we recommend to treat these patients outside the context of this study. Only in case of an increased risk of cardiotoxicity, the HERA study schedule is an alternative, in which case patients could participate in the MATADOR study. Both Arms: For HER2 positive patients with increased risk of cardiotoxicity, who are going to receive trastuzumab according to the schedule of the HERA study, trastuzumab should be given for 52 weeks, and should start within 7 weeks from day 1 of the last chemotherapy cycle or within 6 weeks from the end of adjuvant radiotherapy, whichever is last. Previous interventions until 29/04/2013: 2 randomizations: 1. To one of the treatment arms (TAC or AC dd) 2. To 4 or 6 courses of chemotherapy (second randomization only open for patients with 1-3 positive axillary lymph nodes) AC dd: doxorubicin 60 mg/m2 iv bolus and cyclophosphamide 600 mg/m2 iv bolus on day 1 every 2 weeks. TAC: Docetaxel 75 mg/m2 1 hour i.v. infusion on day 1 in combination with doxorubicin 50 mg/m2 i.v. bolus and cyclophosphamide 500 mg/m2 i.v. bolus on day 1 every 3 weeks. Both Arms: 1. Prophylactic pegfilgrastim 6 mg sc given 1 day
Current inclusion criteria as of 29/04/2013: 1. Women with pT1-T3, pN0-3b, M0 adenocarcinoma of the breast (TNM classification 2002). Women with a macrometastasis in the sentinel node, who did not receive an axillary dissection (pN1(sn)), are only eligible if radiotherapy of the axilla is included in the treatment plan (for instance experimental arm AMAROS study); 2. Known HER2 and estrogen receptor status. 3. Frozen tumor tissue available (or tumor tissue sent in RNAlater to NKI-AVL). 4. primary surgery (defined as date of last surgical intervention) < 6 weeks before randomisation, or radiotherapy < 5 weeks before randomisation. 5. Good performance status (WHO < 1) 6. normal hematology, normal renal and liver function tests (see below). 7. no history of heart failure. 8. Patients of childbearing potential must implement adequate non-hormonal contraceptive measures during study treatment (chemotherapy and hormonal therapy). 9. no conditions that may compromise follow-up. 10. informed consent. 11. At least 18 years old and able to undergo intensive chemotherapy (in the study of Martin et al. employing the TAC regimen (1d) age < 65 years was required). 12. Laboratory requirements: (within 14 days prior to registration) 12.1. Hematology: 12.1.1. Neutrophils ≥ 1.5 109/L; 12.1.2. Platelets ≥ 100 109/L; 12.1.3. Hemoglobin ≥6.0 mmol/L; 12.2. Hepatic function: 12.2.1. Total bilirubin ≤ 16 umol/L; 12.2.2. ASAT (SGOT) and ALAT (SGPT) ≤ 1.5 UNL; 12.2.3. Alkaline phosphatase ≤ 2.5 UNL; 12.3. Renal function: 12.3.1. Creatinine ≤ 120 µmol/L; 12.3.2. If limit values, the calculated creatinine clearance should be ≥ 60 mL/min. Previous inclusion criteria until 29/04/2013: 1. Women with pT0-T3, pN 1-3b, M0 adenocarcinoma of the breast (TNM classification 2002). Women with a macrometastasis in the sentinel node, who did not receive an axillary dissection (pN1(sn)), are only eligible if radiotherapy of the axilla is included in the treatment plan (for instance experimental arm AMAR
Current exclusion criteria as of 29/04/2013: 1. Prior systemic anticancer therapy for any cancer (immunotherapy, hormonal therapy, chemotherapy) 2. Prior radiation therapy for breast cancer 3. HER2 positive breast cancer (except for patients who are going to be treated according to HERA study (1c) 4. Pregnant, or lactating patients 5. Pre-existing motor or sensory neurotoxicity of a severity > grade 2 by NCI criteria 6. Other serious illness or medical condition: 6.1. Congestive heart failure or unstable angina pectoris, previous history of myocardial infarction within 1 year from study entry, uncontrolled hypertension or high-risk uncontrolled arrhythmias 6.2. History of significant neurological or psychiatric disorders including psychotic disorders, dementia or seizures that would prohibit the understanding and giving of informed consent 6.3. Active uncontrolled infection 7. Past history of invasive breast cancer or past or current history of neoplasm other than breast carcinoma, except for: 7.1. Curatively treated non-melanoma skin cancer 7.2. In situ carcinoma of the cervix 7.3. Ipsilateral ductal carcinoma in-situ (DCIS) of the breast 7.4. Lobular carcinoma in-situ (LCIS) of the breast 8. Concurrent treatment with other experimental drugs. Participation in another clinical trial with any investigational not marketed drug within 30 days prior to study entry 9. Male patients Previous exclusion criteria until 29/04/2013: 1. Prior systemic anticancer therapy for any cancer (immunotherapy, hormonal therapy, chemotherapy) 2. Prior radiation therapy for breast cancer 3. Pregnant, or lactating patients 4. Pre-existing motor or sensory neurotoxicity of a severity > grade 2 by NCI criteria 5. Other serious illness or medical condition: 5.1 Congestive heart failure or unstable angina pectoris, previous history of myocardial infarction within 1 year from study entry, uncontrolled hypertension or high-risk uncontrolled arrhythmias 5.2 A history of significant neurologica