Breast Cancer
Conditions
Keywords
stage II breast cancer, stage IIIA breast cancer
Brief summary
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Monoclonal antibodies such as trastuzumab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Radiation therapy uses high-energy x-rays to damage tumor cells. It is not yet known which regimen of chemotherapy plus radiation therapy with or without trastuzumab is more effective in treating breast cancer. PURPOSE: Randomized phase III trial to compare two different chemotherapy regimens plus radiation therapy with or without trastuzumab in treating women who have breast cancer that has spread to lymph nodes in the axilla (under the arm).
Detailed description
OBJECTIVES: * Compare the efficacy of adjuvant cyclophosphamide, epirubicin, and fluorouracil vs adjuvant docetaxel and epirubicin, in terms of 5-year survival without relapse, in women with nonmetastatic adenocarcinoma of the breast with lymph node invasion. * Determine survival of patients treated with these regimens. * Compare the tolerability of trastuzumab (Herceptin) in patients treated with these regimens. * Determine the efficacy and tolerability of trastuzumab in patients with hormone receptor-positive tumors. * Evaluate the quality of life of patients treated with these regimens. OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to participating center. Patients are treated in 2 parts. * Part I: Patients are randomized to 1 of 2 treatment arms. * Arm I: Patients receive fluorouracil IV, or epirubicin IV, and cyclophosphamide IV on day 1. Treatment repeats every 3 weeks for 6 courses. Patients then undergo radiotherapy 5 days a week for 5 weeks. * Arm II: Patients receive epirubicin IV over 10 minutes and docetaxel IV over 1 hour on day 1. Treatment repeats every 3 weeks for 6 courses. Patients then undergo radiotherapy as in arm I. Patients with HER2/neu-positive tumors then proceed to part II. Patients with HER2/neu-negative tumors receive no further treatment. Patients with hormone (estrogen or progesterone) receptor-positive tumors also receive oral tamoxifen daily beginning after chemotherapy is completed and continuing for 5 years. * Part II: Patients are randomized to 1 of 2 treatment arms. * Arm I: Patients receive trastuzumab (Herceptin) IV over 30-90 minutes every 3 weeks for 1 year. * Arm II: Patients are followed without treatment. Patients not receiving trastuzumab are followed at 4 months, 6 months, every 4 months for 1 year, and then every 6 months for 3 years. Patients receiving trastuzumab are followed at 4 months and then every 6 months for 3 years. PROJECTED ACCRUAL: A total of 2,600 patients will be accrued for this study within 3 years.
Interventions
BIOLOGICALTrastuzumab
8 mg/kg at month M6, followed by a maintenance dose of 6 mg/kg every 3 weeks for a 1 year (i.e. 18 injections in total)
DRUGCyclophosphamide
500 mg/m², D1 and every 3 weeks
DRUGdocetaxel
on day D1 of each cycle : dose: 75 mg/m², route: i.v. injection over 1 hour, every 3 weeks
DRUGEpirubicin
100 mg/m², D1 and every 3 weeks
DRUGFluorouracil
500 mg/m², D1 and every 3 weeks
Sponsors
UNICANCER
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 64 Years
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Histologically confirmed nonmetastatic, unilateral adenocarcinoma of the breast * Axillary lymph node invasion (N1, N2, or N3) * No cutaneous invasion * No T4a or greater disease * No clinically or radiologically suspected metastases * No clinically or radiologically suspected contralateral lesion * No deeply adherent or inflammatory disease * Complete surgical resection performed, including removal of at least 5 lymph nodes, and with no residual tumor, within the past 42 days * No prior breast cancer * Hormone receptor status: * Not specified PATIENT CHARACTERISTICS: Age * 18 to 64 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 * ALT and AST no greater than 1.5 times upper limit of normal (ULN) * Alkaline phosphatase no greater than 2.5 times ULN * Bilirubin no greater than ULN * Hepatitis B and hepatitis C negative * No hepatic dysfunction Renal * Creatinine less than 1.3 mg/dL OR * Creatinine clearance greater than 60 mL/min Cardiovascular * ECHO normal * LVEF at least 50% Pulmonary * FEV normal * No dyspnea at rest * No supplemental oxygen dependence Other * Not pregnant * Fertile patients must use effective contraception * HIV negative * No active infection * No other prior malignancy except basal cell skin cancer or carcinoma in situ of the cervix * No contraindication to anthracycline therapy * No chronic medical or psychological condition * No geographic or social reason that would preclude study therapy PRIOR CONCURRENT THERAPY: Biologic therapy * Not specified Chemotherapy * At least 4 weeks since prior chemotherapy * No other concurrent chemotherapy * No contraindication to anthracycline therapy Endocrine therapy * No prior hormonal therapy Radiotherapy * No prior radiotherapy Surgery * See Disease Characteristics Other * At least 4 weeks since prior experimental therapy
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Progression Free Survival | 5 years from randomization |
Secondary
| Measure | Time frame |
|---|---|
| Herceptin safety | 5 years from randomization |
| Overall survival | 5 years from randomization |
Countries
France
Outcome results
None listed