Combination Chemotherapy Compared With Observation After Surgery in Treating Women With Relapsed Nonmetastatic Breast Cancer

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

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.

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.

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