Combination Chemotherapy in Treating Women With Breast Cancer

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug and giving them after surgery may kill any remaining tumor cells following surgery. It is not yet known which combination chemotherapy regimen is more effective in treating breast cancer. PURPOSE: Randomized phase III trial to compare the effectiveness of two different combination chemotherapy regimens in treating women who have primary breast cancer.

Detailed Description
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OBJECTIVES: Compare the time to progression of women with primary breast cancer treated with fluorouracil, epirubicin, and cyclophosphamide vs docetaxel, epirubicin, and cyclophosphamide. Compare the overall survival of patients treated with these regimens. Compare the toxicity of these regimens in these patients. Compare quality of life of patients treated with these regimens. OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to metastatic axillary lymph node involvement (4-9 vs 10 or more), hormone receptor status (estrogen and/or progesterone) of the primary tumor (negative vs positive), and timing of adjuvant radiotherapy (intermittently after completion of 50% of chemotherapy vs after completion of all chemotherapy). Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive fluorouracil IV over 10-15 minutes and epirubicin IV over 15 minutes on days 1 and 8 and oral cyclophosphamide on days 1-14. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. Arm II: Patients receive epirubicin IV over 15 minutes and cyclophosphamide IV over 1 hour on days 1, 21, 42, and 63 and docetaxel IV over 1 hour on days 84, 105, 126, and 147 in the absence of disease progression or unacceptable toxicity. Within 21 days after the completion of chemotherapy, patients undergo adjuvant radiotherapy 5 days a week for 5.5 weeks. Alternatively, patients may undergo radiotherapy intermittently after completion of 50% of chemotherapy. Upon completion of chemotherapy, patients with positive hormone receptor status (estrogen and/or progesterone) receive oral tamoxifen daily for 5 years. Additionally, patients with positive hormone receptor status who are under age 40 receive goserelin subcutaneously every 4 weeks for 2 years. Quality of life is assessed at baseline, prior to each course of chemotherapy, 4 weeks after completion of chemotherapy, 6 weeks after completion of radiotherapy, and then at 6 months after completion of chemotherapy. Patients are followed every 3 months for 3 years, every 6 months for 3 years, and then annually thereafter. PROJECTED ACCRUAL: A total of 446 patients (223 per treatment arm) will be accrued for this study within 3 years.

Official Title
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A Randomized Phase III Trial Comparing FEC-Chemotherapy vs. EC-Doc-Chemotherapy in Patients With Primary Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: cyclophosphamide
* Drug: docetaxel
* Drug: epirubicin hydrochloride
* Drug: fluorouracil
* Drug: goserelin acetate
* Drug: tamoxifen citrate
* Procedure: adjuvant therapy
* Radiation: radiation therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Diagnosis of primary epithelial invasive carcinoma of the breast T1-4, N1-2, M0 Must have 4 metastatic axillary lymph nodes Complete resection of the primary tumor within the past 5 weeks Free of invasive carcinoma with at least 10 lymph nodes removed No inflammatory breast cancer No distant metastases by chest x-ray, liver ultrasound, and whole body bone scan Hormone receptor status: Estrogen and/or progesterone receptor status known PATIENT CHARACTERISTICS: Age 18 to 70 Sex Female Menopausal status Not specified Performance status ECOG 0-1 Life expectancy At least 32 weeks Hematopoietic WBC at least 3,000/mm3 Platelet count at least 100,000 Hepatic Bilirubin no greater than 1.5 times upper limit of normal (ULN) SGOT/SGPT no greater than 1.5 times ULN Alkaline phosphatase no greater than 1.5 times ULN Albumin no greater than 1.5 times ULN Renal Creatinine no greater than 1.5 times ULN Cardiovascular No cardiomyopathy with impaired ventricular function No New York Heart Association class III or IV heart disease No cardiac arrhythmias influencing LVEF and requiring medication No myocardial infarction within the past 6 months No angina pectoris within the past 6 months No uncontrolled arterial hypertension Other No other primary malignancy except carcinoma in situ of the cervix or adequately treated basal cell skin cancer No known hypersensitivity to docetaxel, epirubicin, fluorouracil, cyclophosphamide, or other study medication Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy Not specified Chemotherapy No prior cytotoxic or other antineoplastic therapy No other concurrent cytotoxic or other antineoplastic therapy Endocrine therapy Not specified Radiotherapy No prior radiotherapy Surgery See Disease Characteristics Other At least 3 weeks since prior investigational agents

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: cyclophosphamide|nan|
|Drug: docetaxel|nan|
|Drug: epirubicin hydrochloride|nan|
|Drug: fluorouracil|nan|
|Drug: goserelin acetate|nan|
|Drug: tamoxifen citrate|nan|
|Procedure: adjuvant therapy|nan|
|Radiation: radiation therapy|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of time to progression |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival time |  |  | 
| Toxicity |  |  | 
| Changes in quality of life over time as measured by the EORTC QLQ-C30 and BR23 questionnaires |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage II breast cancer, stage IIIA breast cancer, stage IIIB breast cancer