The regimen PLD plus cyclophosphamide 4 cycles followed by paclitaxel or docetaxel 4 cycles(noted in phase II CAPRICE) will be used as experimental group. The regimen will be compared to the standard treatment of doxorubicin plus cyclophosphamide(AC) 4 cycles followed by paclitaxel or docetaxel 4 cycles\[noted in National Comprehensive Cancer Network (NCCN) guideline\].
Purpose :Anthracycline based chemotherapy regimen is the milestone on the treatment of breast cancer . A sequential protocol, using docetaxel or Paclitaxel after an anthracycline-based combination is primary treatment for high-risk breast cancer .Despite its efficient antitumor activity profile, the use of conventional anthracycline in clinical practice is limited due to it's the risk of cardiac toxicity. The meta analysis show that subclinical cardiotoxicity was 17.9% whereas the incidence of clinically overt cardiotoxicity was 6.3%. Overall cardiovascular events occurred in 10.6%(Lotrisone , Am J Cardiol. 2013).Many patients have healed from breast cancer while they are snatched lives because of heart issue from chemotherapy using anthracycline. There are a lot of clinical trials exploring the possibilities of chemotherapy regimen without anthracycline ,however the recent result has shown anthracycline is indispensible for the patients whose axillary nodes are involved or triple negative breast cancer (ASCO 2016 ).So our target is to find a kind of anthracycline which is of equal efficiency with conventional anthracycline while less cardiac toxicity. Pegylated Liposomal Doxorubicin(PLD) is a novel kind of anthracycline. It distributes into cardiac cells lowly and releases Doxorubicin (DOX) slower to avoid peak plasma concentration, so it is of significant less cardiotoxicity compared to free DOX. It also achieve non-inferior efficacy at 50mg/m2 to conventional anthracycline in Metastatic Breast Cancer (MBC).( M. E. R. O'Brien, ,Annals of Oncology,2004;). PLD 35mg/m2 in combination with paclitaxel showed an overall response rate of 71% ,tolerating toxicity of the skin(3% hand-foot syndrome)and rare cardiac event( H. Gogas1, Annals of Oncology, 2002;Gil-Gil , Breast Cancer Res Treat. 2015)However, There are a crucial question is to know if 35mg/m2 PLD has equivalent efficacy with less cardiac toxicity compared with 60 mg/m2 DOX in adjuvant chemotherapy for all patients. The regimen PLD plus cyclophosphamide 4 cycles followed by paclitaxel or docetaxel 4 cycles(noted in phase II CAPRICE)will be used as experimental group. The regimen will be compared to the standard treatment of doxorubicin plus cyclophosphamide (AC)4 cycles followed by paclitaxel or docetaxel 4 cycles(noted in NCCN guideline). Condition Intervention Phase Individualized Chemotherapy Drug: Pegylated Liposomal Doxorubicin(PLD) Drug: Doxorubicin(DOX) Drug: Cyclophosphamide Drug: docetaxel or Paclitaxel Phase 2 Study Type: Interventional Study Design: Allocation: assignment based on patients desire Endpoint Classification: Safety/Efficacy Study Intervention Model: Marched pair Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
160
35mg/m2 iv drop during the first 4 cycles every three week
600mg/m2 IV drop during the first 4 cycles every three week
100mg/m2 IV drop during the last 4 cycles every three week
First Hospital of Jilin University
Changchun, Jilin, China
RECRUITINGimprovement of pathological complete response（PCR)
Pathological evaluation after sugary
Time frame: at th 26th weeks of treatment since recruitment (after 8 cycles of neoadjuvant chemotherapy when the patient will undergo surgery)
Tolerance according to Common Terminology Criteria Adverse Events (CTCAE) Version 4.0
Cardiogram Cardiac sonography, examination of Cardiac Marker if necessary and Questionaire Survey about Side Effect
Time frame: at 3rd ,6th,9th,12th, 15 ,18,21,24th weeks since recruitment (after each cycle of chemotherapy) ; half year ,1 year , one and half year ,two years since recruitment
Clinical Response Rate
ultrasound of breast and Pathological reports
Time frame: at 3rd ,6th,9th,12th, 15 ,18,21,24th weeks since recruitment （after each cycle of chemotherapy）
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DZR will be administrated for protecting Cardiac toxicity in the group of Active comparator.
Vitamin B will be administrated for protecting HFS in PLD group
60mg/m2 Doxorubicin IV drop during the first 4 cycles every three week
Patients will undergo Breast Conserved Surgery if the tumor/breast ratio is proper and she demands to conserve the breast after 8 cycles of chemotherapy
Patients will undergo Modified Radical Mastectomy if she does not keep her breast after 8 cycles of chemotherapy
Patients will undergo Sentinel Lymph Node Biopsy（SLNB） if the evaluation of lymph node are negative after 8 cycles of chemotherapy