Combination Chemotherapy in Treating Women With Stage I Breast Cancer

Unicancer

Status and phase: Completed; Phase 3

Conditions: Breast Cancer

Treatments: Drug: fluorouracil; Drug: epirubicin hydrochloride; Drug: cyclophosphamide

Study type: Interventional

Funder types: Other

Identifiers

NCT00055679

FRE-FNCLCC-PACS-05/0106

EU-20239

PACS05 UC-0140-0106

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 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.

Full description

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.

Enrollment: 1,512 patients

Sex: Female

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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1,512 participants in 2 patient groups

6 FEC

Active Comparator group

Description:

6 cycles of CYCLOPHOSPHAMIDE + EPIRUBICINE + 5-FLUOROURACILE

Treatment:

Drug: fluorouracil

Drug: cyclophosphamide

Drug: epirubicin hydrochloride

4 FEC

Experimental group

Description:

4 cycles of CYCLOPHOSPHAMIDE + EPIRUBICINE + 5-FLUOROURACILE

Treatment:

Drug: fluorouracil

Drug: cyclophosphamide

Drug: epirubicin hydrochloride