Combination Chemotherapy Compared With Observation After Surgery in Treating Women With Relapsed Nonmetastatic 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 whether combination chemotherapy is more effective than observation in treating relapsed nonmetastatic breast cancer. PURPOSE: Randomized phase III trial to compare the effectiveness of combination chemotherapy with that of observation in treating women who have undergone surgery for relapsed nonmetastatic breast cancer.

Detailed Description
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OBJECTIVES: Compare the efficacy of adjuvant cyclophosphamide, epirubicin, and fluorouracil vs observation, in terms of disease-free 5-year survival, in women who have undergone resection for relapsed nonmetastatic breast cancer after initial conservative surgery. Compare the overall survival of women treated with these regimens. Determine the tolerance of these women to the chemotherapy regimen. Correlate prognostic factors of survival with efficacy of the chemotherapy regimen in these women. OUTLINE: This is a randomized, multicenter study. Patients are stratified according to menopausal status and participating center. Patients are randomized to 1 of 2 treatment arms. Study begins within 42 days after resection of recurrent disease. Arm I: Patients receive fluorouracil IV over 1 hour, epirubicin IV over 1 hour, and cyclophosphamide IV over 1 hour on day 1. Treatment repeats every 3 weeks for 3 courses in the absence of disease progression or unacceptable toxicity. Patients then receive docetaxel IV over 1 hour on day 1. Treatment repeats every 3 weeks for 3 courses in the absence of disease progression or unacceptable toxicity. Arm II: Patients are examined on days 1 and 63. Patients who are hormone receptor positive also receive one of the following hormonal therapy regimens, depending on menopausal status: Oral tamoxifen daily for 5 years Oral tamoxifen daily for 5 years and oral luteinizing hormone-releasing hormone (LHRH) agonist therapy (e.g., goserelin) for 3 years Oral LHRH agonist therapy (e.g., goserelin) for 3 years Oral antiaromatase therapy (e.g., anastrozole) for 5 years Patients also undergo radiotherapy and may also undergo second complete resection. Patients are followed every 6 months for 5 years and then annually thereafter. PROJECTED ACCRUAL: A total of 370 patients (185 per treatment arm) will be accrued for this study within 3 years.

Official Title
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Randomized And Multicentric Phase III Study Evaluating The Benefit By Using A Chemotherapy With FEC 100 And Docetaxel In Non Metastatic Breast Cancer Which Has Relapsed After A Conservative Surgery

Conditions
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Breast Cancer

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


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed adenocarcinoma of the breast No contralateral breast cancer Local tumor recurrence more than 6 months after conservative surgery Complete or conservative resection of the recurrent tumor NOTE: Initial complete surgical resection not allowed No local inflammatory disease or disease that is not amenable to complete surgical resection No positive axillary lymph nodes No distant metastases, including subclavicular lymph nodes Hormone receptor status: Hormone receptor status known PATIENT CHARACTERISTICS: Age 18 to 65 Sex Female Menopausal status Menopausal status known Performance status ECOG 0-1 Life expectancy Not specified Hematopoietic Neutrophil count at least 2,000/mm^3 Platelet count at least 100,000/mm^3 Hepatic Bilirubin no greater than upper limit of normal (ULN) Transaminases no greater than 1.5 times ULN Alkaline phosphatase no greater than 2.5 times ULN No chronic hepatitis B No active hepatitis C Renal Not specified Cardiovascular Cardiac function normal by echocardiogram or isotopes Other No contraindications to anthracyclines such as any of the following: Prior doxorubicin over 300 mg/m^2 Prior epirubicin over 600 mg/m^2 Prior mitoxantrone over 90 mg/m^2 No other invasive malignancy No chronic somatic or psychiatric condition that would preclude study participation No familial, social, geographic, or psychological reason that would preclude study participation Not pregnant Fertile patients must use effective contraception HIV negative CA 153 no greater than 2 times ULN PRIOR CONCURRENT THERAPY: Biologic therapy Not specified Chemotherapy See Patient Characteristics-Other No prior neoadjuvant chemotherapy Endocrine therapy No prior neoadjuvant hormonal therapy Radiotherapy No prior neoadjuvant radiotherapy Surgery See Disease Characteristics At least 41 days since prior surgery

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


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: anastrozole|nan|
|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|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of the disease free survival |  | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of the overall survival |  | 5 years | 

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