Efficacy and Safety of Neoadjuvant DC-T in Breast Cancer Patients

OBJECTIVES: Determine the efficacy and safety of neoadjuvant chemotherapy regimen DC-T and EC-T in suitable breast cancer patients.

Participants are randomized to 1 of 2 treatment arms.

1. Arm I: Participants receive pegylated liposomal doxorubicin plus cyclophosphamide followed by docetaxel before surgery.
2. Arm II: Participants receive epirubicin plus cyclophosphamide followed by docetaxel before surgery.

Patients in arms I and II will undergo physical examination, MRI, estimating of side effects every 4 cycles referring to RECIST (Response Evaluation Criteria In Solid Tumor) guideline. To adjust for potential bias, patients in DC-T arm were matched 1:1 to patients in the EC-T arm based on Her-2 and ER status. After finishing 8 cycles of neoadjuvant chemotherapy, every patient will receive mastectomy or breast-conserving surgery and then assess the pCR rate of primary lesion and axillary lymph nodes. Adjuvant radiotherapy and endocrine therapy will be taken if necessary. Every patient will be followed-up for five years to monitor survival condition.

• Pegylated liposomal doxorubicin (Drug), also known as PLD: a new kind of doxorubicin
• Cyclophosphamide (Drug), also known as C: traditional chemotherapy drug
• Epirubicin (Drug), also known as E: traditional chemotherapy drug used in breast cancer
• Docetaxel (Drug), also known as T: traditional chemotherapy drug used in breast cancer

Primary outcomes

• Pathological complete response rate [5 years]: The pathological complete response rate of primary lesion and axillary lymph nodes

Secondary outcomes

• Side effects [5 years]: Determine side effects of these drugs like cardiotoxicity ,hematological toxicity，gastrointestinal symptoms and so on.
• Overall survival [5 years]: Determine the overall survival at 5 years.

Sex: Female, ages: 18 Years to 70 Years

Inclusion Criteria:

1. Women aged : 18\~70 years.
2. WHO (ECOG) performance status 0-2.
3. Patients who have read and understand the informed consent form and have given written informed consent.
4. Diagnosed as invasive breast cancer by core biopsy
5. Diagnosed pre-surgically as (cTNM Staging)Stage II-III and suit for neoadjuvant chemotherapy.
6. Patients had previously not received chemotherapy，radiotherapy or biotherapy.
7. Normal organ function，meeting the requirement of laboratory testing below:

   * WBC≥4.0×109/L,
   * NEU≥1.5×109/L,
   * PLT≥100×109/L,
   * HB ≥10g/dL,
   * Scr≤1.5× ULN,
   * AST ≤2.5×ULN,
   * ALT ≤2.5×ULN,
   * TDIL≤1.5×ULN.
8. Patients with measurable lesion assessed by imaging using the RECIST (Response Evaluation Criteria In Solid Tumor) guideline，（long diameter of primary lesion ≥1cm or minor diameter of lymph node ≥1.5cm）；

Exclusion Criteria:

1. Pregnant or lactating women were excluded.
2. History of receiving organ transplantation（including Autologous bone marrow transplantation and peripheral hematopoietic stem-cell transplantation).
3. Dysfunction of peripheral nerve system caused by other diseases or history of either severe mental disorder or central nervous system disorders.
4. Uncontrolled infection or severe peptic ulcer need treatment.
5. Severe hepatic disease（such as hepatic cirrhosis),nephrosis,respiratory disease or uncontrolled diabetes.
6. Patients with malignancies (other than breast cancer) within the last 5 years, except for adequately treated in situ carcinoma of the cervix or basal cell carcinoma of the skin.
7. Significant abnormal EKG or cardiac disease with drastic symptoms like congestive heart failure or severe coronary disease or uncontrolled arrhythmia or myocardial infarction within 12 months or NYHA level III-IV or LVEF<55% .
8. Be allergic to test drugs.

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• Huang Jian, Dr, Study chair, Second Affiliated Hospital of Zhejiang University School of Medicine