Doxorubicin and Cyclophosphamide (AC) Followed by Weekly Docetaxel as Neoadjuvant Treatment of Breast Cancer Patients
Doxorubicin and Cyclophosphamide (AC) Followed by Weekly Docetaxel as Neoadjuvant Treatment of Breast Cancer Patients
Treatment consists of 4 AC cycles followed by 2 weekly docetaxel cycles (12 infusions).

 The pathological complete response rate obtained in previous studies is around 12%. The
 expected pathological complete response rate in this study is 25%. With an alpha error of
 0.05 and a beta error of 0.2, and following Simon´s 2 phase test, 19 patients are needed
 initially. With 2 pathological complete responses, patient recruitment will continue until
 approximately 61 patients are recruited. Twelve pathological complete responses are needed to
 confirm the study hypothesis.
Patients received doxorubicin (60 mg/m2) and cyclophosphamide (600 mg/m2), both in a short
 intravenous infusion, every three weeks for four cycles (days 1, 22, 43 and 64). Three weeks
 later, docetaxel (36 mg/m2) was administered as a 30-min intravenous infusion, weekly for six
 weeks (days 85, 92, 99, 106, 113 and 120) followed by a 2-week resting period (8-week cycle).
 After that, patients received a second docetaxel cycle (infusions on days 141, 148, 155, 162,
 169 and 176). Adjuvant chemotherapy and radiotherapy were delivered according to the protocol
 of each participating center. Hormonal treatment was started after the last chemotherapy
 infusion in all patients with positive estrogen and/or progesterone receptor tumors and was
 continued for five years.

 Semiquantitative determination of three molecular markers was carried out by
 immunocytochemical methods. Tissue samples were taken prior to initiation of chemotherapy
 from the core of the primary tumors. Specimens were sent to a central laboratory for analysis
 of Topo II, survivin and p27.
Inclusion Criteria:

 -  Written informed consent.

 -  Patients with breast cancer stages II and IIIA, with histological diagnoses as per
 true-cut or open biopsy.

 -  Negative extension study, including bilateral mammography, thoracic x-ray, computed
 tomography (CT)-scan or abdominal echography and bone scintigraphy.

 -  Analysis of hormone receptor status in primary tumour. It is highly recommended to
 obtain a tumour tissue sample before start of treatment, and after definitive surgery.
 These samples will be analysed centrally by Spanish Breast Cancer Research Group
 (GEICAM).

 -  Age >= 18 and <= 70 years old.

 -  Performance status as per Karnofsky index >= 80.

 -  Minimum life expectancy of 6 months.

 -  Electrocardiogram (EKG) 12 weeks before registration to the study. If abnormalities
 are suspected, cardiac function must be assessed by left ventricular ejection fraction
 (LVEF).

 -  Haematology: neutrophils >= 2.0 x10^9/l; platelets >= 100 x10^9/l; hemoglobin >=10
 g/dl.

 -  Hepatic function: total bilirubin <= 1 x upper normal limit (UNL); Aspartate
 aminotransferase (AST) (SGOT) and and Alanine aminotransferase (ALT) (SGPT) <= 2.5 x
 UNL; alkaline phosphatase <= 5 x UNL.

 -  Renal function: creatinine <= 1.5 x UNL; creatinine clearance >= 60 ml/min.

 -  Patients able to comply with study requirements.

 -  Negative pregnancy test.

 -  Adequate contraceptive method during the study and up to 3 months after definitive
 surgery.

 Exclusion Criteria:

 -  Previous systemic therapy for breast cancer treatment.

 -  Previous treatments with anthracyclines or taxanes for any malignancy.

 -  Previous radiotherapy for breast cancer.

 -  Bilateral invasive breast cancer.

 -  Pregnant or lactating women.

 -  Previous motor or sensorial neurotoxicity grade >=2.

 -  Other serious pathologies: congestive heart failure or angina pectoris; history of
 myocardial infarction in the previous year; uncontrolled hypertension (HT) or high
 risk arrhythmias.

 -  History of neurological or psychiatric impairment, precluding patients from providing
 free informed consent.

 -  Active infection.

 -  Active peptic ulcer; unstable diabetes mellitus.

 -  History of previous or current malignancies other than breast cancer, except for basal
 skin carcinoma, cervical in situ carcinoma, other tumour diagnosed and treated more
 than 10 years before, ductal carcinoma in situ (DCIS) or lobular carcinoma in situ
 (LCIS).

 -  Chronic treatment with corticoids unless the treatment started > 6 months before
 registration to the study, and low doses are administered.

 -  Substitutive hormonal therapy. This treatment must be interrupted before inclusion in
 the study.

 -  Concomitant treatment with other investigational products or administration in the 30
 previous days.

 -  Males.