Preoperative Epirubicin Paclitaxel Aranesp Study (PREPARE)
Preoperative Epirubicin Paclitaxel Aranesp Study (PREPARE)
The present clinical trial will investigate the efficacy of a sequential interval-shortened
 and dose-intensified preoperative use of epirubicin, paclitaxel and CMF with preoperative
 sequential administration of epirubicin and cyclophosphamide followed by paclitaxel in breast
 cancer. In addition, the influence of darbepoetin alfa on the response rate and quality of
 life is to be investigated in both treatment arms.
Arm A: Sequential treatment in standard doses with Epirubicin (90 mg/m2)/cyclophosphamide
 (600 mg/m2) d1, q21d - 4× followed by paclitaxel (175 mg/m2) d1, q21d - 4×.

 Pegfilgratim should be used as secondary preventive after febrile neutropenia in the standard
 arm of the study, or in exceptional cases also after severe febrile neutropenia necessitating
 postponement of the treatment by more than one week ± Darbepoetin alfa 1 × 4.5 µg/kg of body
 weight every two weeks with the start of the first epirubicin dose (day 1) until 14 days
 after the last dose of paclitaxel Daily oral intake of 200 mg iron unless there complications
 occur with taking iron

 Arm B: sequential dose-intensified, interval-shortened treatment with Epirubicin (150 mg/m2)
 d1, q14d - 3× followed by paclitaxel (225 mg/m2) d1, q14d - 3×, followed by CMF (600/40/600
 mg/m2) d1/d8, q28d - 3× Obligatory pegfilgratim 6 mg after epirubicin and/or paclitaxel:
 subcutaneous injection on day 2. After CMF pegfilgrastim should be used as a secondary
 preventive measure

 ± Darbepoetin alfa 1 × 4.5 µg/kg of body weight every two weeks with the start of the first
 dose of epirubicin (day 1) until 14 days after the last dose of CMF Daily oral dose of 200 mg
 iron unless complications occur in taking iron.

 Primary goal: Determining the relapse-free survival time and overall survival after
 dose-intensified sequential preoperative chemotherapy including anthracycline and taxan
 and/or after preoperative chemotherapy including anthracycline followed by taxan in a
 standard dose
Inclusion Criteria:

 -  Histologically confirmed breast cancer: at least three fast biopsies.

 -  Primary tumor ≥2 cm acc. to clinical measurement or manifestation of an inflammatory
 breast cancer.

 -  No systemic metastasis, exclusion by chest x-ray, sonogram of the upper abdomen and
 skeletal scintiscan.

 -  Age ≥18 years and ≤65 years.

 -  ECOG < 2/WHO 0-1

 -  Adequate organ function defined as SGOT and bilirubin ≤ 1.5× upper limit WBC ≥ 3000
 /µL Neutrophils ≥ 1000 /µL Platelets ≥ 100,000 /µL Serum creatinine < 2.0 mg/dL

 -  Unremarkable heart echo

 -  No florid hepatitis

 -  Written consent to participate in the treatment optimization protocol

 Exclusion Criteria:

 -  Multicentricity in various quadrants (contact the study office)

 -  Known allergy to E. coli-produced medication

 -  Known allergy to medication containing cremophor (e.g., cyclosporin A)

 -  Patients receiving immunosuppressant therapy

 -  Lack of consent after informing the patient

 -  Lack of willingness to keep and disclose personal medical data as part of the study

 -  Pregnancy, nursing

 -  Secondary malignancy, excluding basalioma of the skin or carcinoma in situ of the
 cervix that has received curative therapy

 -  Pre-existing treatment-resistant cardiac disease, coronary heart disease, arrhythmias,
 cardiac insufficiency

 -  Patients with uncontrolled hypertension (diastolic >95 mmHg)

 -  A history of convulsions

 -  Known hypersensitivity to darbepoetin alfa or any of its other ingredients or a known
 hypersensitivity to r-HuEPO