Minus Anthracycline or Short-Term Versus Epirubicin and Cyclophosphamide Followed by Paclitaxel Regimen for Adjuvant Breast Cancer Therapy

Study Overview
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Brief Summary
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We aimed to evaluate the noninferiority of short-term anthracycline-free chemotherapy (TC, six cycles of docetaxel and cyclophosphamide) or short-term anthracycline-based chemotherapy (CEF-T, three cycles of cyclophosphamide/epirubicin/fluorouracil followed by three cycles of docetaxel) to a standard anthracycline/taxane-containing chemotherapy (EC-P, epirubicin, and cyclophosphamide for four cycles followed by paclitaxel for twelve weeks) in HER2-negative operable breast cancer.

Detailed Description
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It was initiated as an adjuvant chemotherapy trial to test noninferiority of an anthracycline-free short-term regimen (T75C600 x 6 [TC] once every 3 weeks) or a short-term regimen (C500E100F500 x 3 once every 3 weeks followed by T100 x 3 every 3 weeks [CEF-T]) compared with a standard long-term anthracycline-containing regimen (E90C600 x 4 once every 3 weeks followed by P80 x 12 once every week [EC-P]) in HER2-negative breast cancer. Patients were randomly assigned (1:1:1) to each arm after completing the surgical excision of the primary tumor.

Official Title
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Adjuvant 6 Cycles of Docetaxel and Cyclophosphamide or 3 Cycles of Cyclophosphamide/Epirubicin/Fluorouracil Followed by 3 Cycles of Docetaxel Versus 4 Cycles of Epirubicin and Cyclophosphamide Followed by Weekly Paclitaxel in HER2-negative Operable Breast Cancer

Conditions
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Primary Breast Cancer

Intervention / Treatment
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* Drug: Docetaxel Cyclophosphamide
* Drug: Cyclophosphamide Fluorouracil Epirubicin Docetaxel
* Drug: Epirubicin Cyclophosphamide Paclitaxel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female patients, age at diagnosis 18 - 75 years Histological confirmed unilateral primary invasive carcinoma of the breast Adequate surgical treatment with complete resection of the tumor (R0) and resection of > or = 10 axillary nodes or SLN in clinically N0 patients Node positive disease or node-negative disease with at least one other risk factor (tumor size > or = 2 cm, grade > or = II) HER2-negative disease No evidence for distant metastasis (M0) after conventional staging Performance Status ECOG < or = 1 The patient must be accessible for treatment and follow-up LVEF> 50% Negative pregnancy test (urine or serum) within 7 days prior to randomization in premenopausal patients Leucocytes > or = 4 x 10^9/L platelets > or = 100 x 10^9/L haemoglobin > or = 9 g/dL total bilirubin < or = 1.5 UNL ASAT (SGOT) and ALAT (SGPT) < or = 2.5 UNL creatinine < 175 mmol/L (2 mg/dL) Exclusion Criteria: Has received neoadjuvant therapy (include chemotherapy, targeted therapy, radiotherapy or endocrine therapy）; Has bilateral breast cancer; Has the previous history of additional malignancy, with the exception of adequately treated basal cell carcinoma and cervical carcinoma in situ. Has metastatic (Stage 4) breast cancer; Has any >T4 lesion (UICC1987) (with skin involvement, mass adhesion and fixation, and inflammatory breast cancer); Is pregnant, is breastfeeding women, or women of childbearing age who cannot practice effective contraceptives; Patients participating in other clinical trials at the same time; Has severe organ dysfunction (cardiopulmonary liver and kidney) insufficiency, left ventricular ejection fraction (LVEF) < 50% (cardiac ultrasound); severe cardio cerebral vascular disease within the 6 months previous of randomization (such as unstable angina, chronic heart failure, uncontrolled hypertension with blood pressure>150/90mmgh, myocardial infarction, or cerebral blood vessel); diabetic patients with poor blood glucose control; patients with severe hypertension; Has known allergy to taxane and excipients; Has severe or uncontrolled infection.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TC*6<br>6 cycles of (Docetaxel 75mg/m2 ivgtt d1+ Cyclophosphamide 600 mg/m2 iv d1, 21 days per cycle) . | Drug: Docetaxel Cyclophosphamide<br>* Docetaxel 75 mg/m² D1 Cyclophosphamide 600 mg/m² D1 1 cycle = 21 days TC*6<br>|
| Experimental: CEF*3-T*3<br>3 cycles of CEF (Epirubicin 100 mg/m2 ivgtt d1+Cyclophosphamide 500 mg/m2 iv d1+ 5-fluorouracil 500 mg/m2 iv d1, 21 days per cycle) followed by 3 cycles of Docetaxel (Docetaxel 100mg/m2, ivgtt d1, 21 days per cycle) | Drug: Cyclophosphamide Fluorouracil Epirubicin Docetaxel<br>* 1st -3rd Cycle: Fluorouracil 500 mg/m² D1 Epirubicin 100 mg/m² D1 Cyclophosphamide 500 mg/m² D1 1 cycle = 21 days 4th-6th Cycle: Docetaxel 100mg/m² D1 1 cycle = 21 days CEF*3-T*3<br>|
| Experimental: EC*4-wP*12<br>4 cycles of EC (Epirubicin 90 mg/m2 ivgtt d1+Cyclophosphamide 600 mg/m2 iv d1, 21 days per cycle) followed by 4 cycles of Paclitaxel (Paclitaxel 80mg/m2, ivgtt d1,8,15, 21days per cycle) | Drug: Epirubicin Cyclophosphamide Paclitaxel<br>* 1st-4th Cycle: Epirubicin 90 mg/m² D1 Cyclophosphamide 600 mg/m² D1 1 cycle = 21 days 5th-8th Cycle: Paclitaxel 80mg/m² D1, 8, 15 1 cycle = 21 days EC*4-P*4<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease-Free Survival | Defined as the time from randomization to occurrence of a new event including local recurrence, regional relapse, distant metastasis, contralateral primary breast cancer, second non-breast invasive cancer (excluding non-melanoma skin cancers), or death from any cause. | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Distant Disease-Free Survival | Defined as the time from randomization to the earliest recurrence outside of the ipsilateral locoregional region or to death from any cause, whenever a death occurred before distant recurrence | 5 years | 
| Overall Survival | defined as the time from randomization to death from any cause | 5 years | 
| Adverse Events | Number of Participants with Adverse Events | through chemotherapy completion, an average of 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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TNBC, OS, Luminal A, Luminal B, DFS, DDFS