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.

PURPOSE: This randomized phase II trial is studying three regimens of combination chemotherapy to compare how well they work in treating women with stage I or stage II breast cancer.

Condition	Treatment or Intervention	Phase
stage I breast cancer stage II breast cancer	Drug: cyclophosphamide  Drug: doxorubicin  Drug: epirubicin  Drug: mitoxantrone  Drug: vinorelbine  Procedure: chemotherapy  Procedure: conventional surgery  Procedure: radiation therapy  Procedure: surgery	Phase II

Further Study Details: 

OBJECTIVES:

• Determine the efficacy of vinorelbine/epirubicin and vinorelbine/mitoxantrone in terms of clinical objective tumor response, clinical complete remission, and pathological complete remission in women with early stage breast cancer.
• Compare the efficacy of these 2 new regimens with an established regimen of cyclophosphamide/doxorubicin in a randomly selected control group of patients.
• Compare the toxicity and side effects of these 2 new regimens in these patients.

OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to center and age (under 50 vs 50 and over). Patients are randomized to one of three treatment arms.

• Arm I: Patients receive vinorelbine IV on days 1 and 8 and epirubicin IV on day 1.
• Arm II: Patients receive vinorelbine IV on days 1 and 8 and mitoxantrone IV on day 1.
• Arm III: Patients receive doxorubicin IV and cyclophosphamide IV on day 1. Treatment continues every 3 weeks for 6 courses in the absence of unacceptable toxicity or disease progression. All patients except those who are under 50 and whose tumors are estrogen receptor negative receive oral adjuvant tamoxifen daily in addition to chemotherapy.

All patients are offered surgery following completion of chemotherapy. Radiotherapy begins within 4 weeks of completion of chemotherapy or surgery, whichever is the immediately preceding treatment.

Patients are followed every 3 months for the first 2 years, every 6 months for the next 3 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 62-125 patients will be accrued for this study within 12-18 months.

Ages Eligible for Study:  18 Years   -   70 Years,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed primary breast cancer that is potentially operable
• Synchronous bilateral tumors eligible
• At least 3 cm in maximum diameter
• Tumors at least 2 cm eligible provided primary chemotherapy is deemed appropriate and radical surgery would otherwise be required
• No evidence of metastatic disease
• No prior breast cancer
• Hormone receptor status:
• Not specified

PATIENT CHARACTERISTICS: Age:

• 18 to 70

Sex:

• Female

Menopausal status:

• Not specified

Performance status:

• WHO 0-1

Life expectancy:

• Not specified

Hematopoietic:

• WBC at least 3,000/mm^3
• Platelet count at least 150,000/mm^3

Hepatic:

• Bilirubin no greater than 1.5 times upper limit of normal (ULN)
• Transaminases no greater than 1.5 times ULN

Renal:

• Creatinine no greater than 1.5 times ULN

Cardiovascular:

• No uncontrolled angina pectoris
• No heart failure
• No clinically significant uncontrolled cardiac arrhythmias
• LVEF at least 50%

Other:

• Not pregnant or nursing
• Fertile patients must use effective contraception
• No medical or psychiatric condition that impairs ability to cope physically or psychologically with the chemotherapy regimen
• No other serious uncontrolled medical condition
• No other prior malignancy except basal cell carcinoma of the skin or carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

United Kingdom, England
      Royal Marsden NHS Foundation Trust - Surrey, Sutton,  England,  SM2 5PT,  United Kingdom; Recruiting

Study chairs or principal investigators

Ian Edward Smith, MD,  Study Chair,  Royal Marsden NHS Trust   

Study ID Numbers:  CDR0000067481; RMNHS-TOPIC2; EU-99037; NCT00004237
Record last reviewed:  February 2000
Last Updated:  February 24, 2005
Record first received:  January 28, 2000
ClinicalTrials.gov Identifier:  NCT00004237
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08