Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Antineoplastic Agents

Antirheumatic Agents

All Drugs and Chemicals

Micronutrients

Cardiotonic Agents

Hematinics

Anti-Infective Agents

Vitamins

Cyclophosphamide

Doxorubicin

Liposomal doxorubicin

Docetaxel

Vitamin B Complex

Dexrazoxane

Razoxane

Pirarubicin

Folic Acid

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Trace Elements

Tubulin Modulators

Antimitotic Agents

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

Protective Agents

Folate

Vitamin B9

AC-T regimen 8 cycles ,60mg/M2 conventional Doxorubicin will be used as active comparator. four cycles of Doxorubicin plus 600mg/m2 Cyclophosphamide every three weeks followed 4 cycles of 100mg/m2 Taxotere, every three weeks for one cycle.Dexrazoxane (DZR)will be used for protecting cardiac toxicity.Patients will undergo Modified Radical Mastectomy or Breast Conserved Surgery or Axillary Lymph Node Dissection(ALND) or Sentinel Lymph Node Biopsy（SLNB） after 8 cycles of chemotherapy

Pegylated Liposomal Doxorubicin(PLD) plus Cyclophosphamide followed Taxotere 8 cycles.35mg/M2 PLD will be used as experimental medicine. four cycles of PLD plus 600mg/m2 Cyclophosphamide every three weeks followed 4 cycles of 100mg/m2 Taxotere , every three weeks for one cycle.Vitamin B will be used for protecting hand-foot syndrome(HFS).Patients will undergo Modified Radical Mastectomy or Breast Conserved Surgery or Axillary Lymph Node Dissection(ALND) or Sentinel Lymph Node Biopsy（SLNB） after 8 cycles of chemotherapy

35mg/m2 iv drop during the first 4 cycles every three week

Pegylated Liposomal Doxorubicin

600mg/m2 IV drop during the first 4 cycles every three week

100mg/m2 IV drop during the last 4 cycles every three week

Taxotere

DZR will be administrated for protecting Cardiac toxicity in the group of Active comparator.

Dexrazoxane (DZR)

Vitamin B will be administrated for protecting HFS in PLD group

vitamin B

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

Breast Conserved Surgery

Patients will undergo Modified Radical Mastectomy if she does not keep her breast after 8 cycles of chemotherapy

Modified Radical Mastectomy

Patients will undergo Sentinel Lymph Node Biopsy（SLNB） if the evaluation of lymph node are negative after 8 cycles of chemotherapy

Sentinel Lymph Node Biopsy（SLNB）

Di Wu, Doctor

Hongyao Jia, Master

Aiping Shi, Doctor

Zhimin Fan, Doctor

Xin Guan, Master

Haibo Wang, Doctor

Gang Nie, Doctor

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

Marched Pair Study Conventional Doxorubicin(DOX) Versus Pegylated Liposomal Doxorubicin(PLD) Neoadjuvant Chemotherapy

Marched Pair Study of the Standard Chemotherapy 4doxorubicin Plus Cyclophosphamide(AC) 60 + 4 Docetaxel Protocol Versus 4 PLD C35+4 Docetaxel in Neoadjuvant Chemotherapy of Breast Cancer

Cardiogram Cardiac sonography, examination of Cardiac Marker if necessary and Questionaire Survey about Side Effect

ultrasound of breast and Pathological reports

Spots Global Cancer Trial Database for breast conserved surgery