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

Unicancer

Status and phase

Terminated

Phase 3

Conditions

Breast Cancer

Treatments

Drug: tamoxifen citrate

Drug: cyclophosphamide

Procedure: adjuvant therapy

Drug: epirubicin hydrochloride

Drug: docetaxel

Drug: anastrozole

Drug: goserelin acetate

Drug: fluorouracil

Study type

Interventional

Funder types

Other

Identifiers

NCT00053911

PACS03

FRE-FNCLCC-PACS-03/003

EU-20237

Details and patient eligibility

About

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.

Full description

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.

Sex

Female

Ages

18 to 65 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

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