Combination Chemotherapy in Treating Women With Stage I 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 may kill more tumor cells. It is not yet known which combination chemotherapy regimen is more effective in treating early breast cancer. PURPOSE: Randomized phase III trial to determine the effectiveness of different regimens of combination chemotherapy in treating women who have stage I breast cancer.

Detailed Description
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OBJECTIVES: Compare the efficacy of 4 vs 6 courses of adjuvant fluorouracil, epirubicin, and cyclophosphamide, in terms of 5-year survival, in women with stage I breast cancer. Compare the toxicity of these regimens in these patients. Determine the correlation of length of survival with biological factors in patients treated with these regimens. Determine biological factors significant for prognosis and prediction of survival of patients treated with these regimens. Determine the overall survival of patients treated with these regimens. OUTLINE: This is a randomized, open-label, multicenter study. Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive fluorouracil IV, epirubicin IV, and cyclophosphamide IV on day 1. Treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. Arm II: Patients receive the same regimen as in arm I for up to 4 courses. After completion of chemotherapy, patients undergo radiotherapy 5 days a week for 6 weeks. Patients who are estrogen or progesterone receptor positive also receive oral tamoxifen daily for 5 years, beginning after completion of chemotherapy. Patients are followed every 6 months for 5 years. PROJECTED ACCRUAL: A total of 1,512 patients (756 per treatment arm) will be accrued for this study within 3 years.

Official Title
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Phase III Randomized Study Of Adjuvant Fluourouracil, Epirubicin And Cyclophosphamide, In Women With Stage I Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: cyclophosphamide
* Drug: epirubicin hydrochloride
* Drug: fluorouracil


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed nonmetastatic, unilateral adenocarcinoma of the breast Stage I No clinically or radiologically suspicious metastases No positive sentinel lymph nodes by immunohistochemistry for tumors less than 2 cm No clinically proven positive axillary lymph nodes Tumor cells found on immunohistochemistry only allowed No clinically or radiologically contralateral suspicious lesions No deeply adherent disease No cutaneous invasion No inflammatory disease Complete surgical resection within the past 42 days At least 8 lymph nodes removed Tumor at least 1 cm with no residual disease Presenting with at least 1 of the following factors of a poor prognosis: Tumor greater than 2 cm Hormone receptor negative tumor Grade II or III 35 years old or under Hormone receptor status: Positive or negative PATIENT CHARACTERISTICS: Age 18 to 65 Sex Female Menopausal status Not specified Performance status WHO 0-1 Life expectancy Not specified Hematopoietic WBC at least 2,000/mm^3 Platelet count at least 100,000/mm^3 Hepatic Bilirubin no greater than 1.25 times upper limit of normal (ULN) AST and ALT no greater than 1.25 times ULN Alkaline phosphatase no greater than 2.5 times ULN No chronic hepatitis B No active hepatitis C Renal Creatinine no greater than 1.25 times ULN Pulmonary FEV normal Other Not pregnant or nursing HIV negative No prior breast cancer or other malignancy No familial, social, or geographical reason that would preclude study participation PRIOR CONCURRENT THERAPY: Biologic therapy Not specified Chemotherapy No prior chemotherapy Endocrine therapy No prior anticancer hormone therapy Radiotherapy No prior radiotherapy Surgery See Disease Characteristics

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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 |
| --- | --- |
| Active Comparator: 6 FEC<br>6 cycles of CYCLOPHOSPHAMIDE + EPIRUBICINE + 5-FLUOROURACILE | Drug: cyclophosphamide<br> <br> Drug: epirubicin hydrochloride<br> <br> Drug: fluorouracil<br> <br> |
| Experimental: 4 FEC<br>4 cycles of CYCLOPHOSPHAMIDE + EPIRUBICINE + 5-FLUOROURACILE | Drug: cyclophosphamide<br> <br> Drug: epirubicin hydrochloride<br> <br> Drug: fluorouracil<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy, in terms of 5-year survival |  | 5 years from randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Event free survival |  | 5 years from randomization | 
| Toxicity |  | 5 years from randomization | 
| Biological factors significant for prognosis and prediction of survival |  | 5 years from randomization | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage I breast cancer