Comparison of Two Combination Chemotherapy Regimens in Treating Women With Breast Cancer
RATIONALE: Drugs used in chemotherapy, such as fluorouracil, epirubicin, cyclophosphamide, and doxorubicin, work in different ways to stop tumor cells from dividing so they stop growing or die. It is not yet known which combination chemotherapy regimen is more effective in treating breast cancer.
PURPOSE: This randomized phase III trial is studying two combination chemotherapy regimens to compare how well they work in treating women who have undergone surgery for breast cancer that has not spread to the lymph nodes.
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Clinical Trial Of Adjuvant Therapy Comparing Six Cycles Of 5-Fluorouracil, Epirubicin And Cyclophosphamide (FEC) To Four Cycles Of Adriamycin And Cyclophosphamide (AC) In Patients With Node-Negative Breast Cancer|
- Disease free survival or no breast cancer (BC) at time of local recurrence (LR) after mastectomy, LR in the ipsilateral breast following lumpectomy, regional or distant recurrence, contralateral BC, 2nd primary cancer, or death [ Time Frame: Time from randomization to local recurrence regional recurrence, distant recurrence, contralateral BC, second primary cancer or death from any cause prior to recurrence or second primary cancer. ]
- Survival [ Time Frame: Time from randomization to any death ]
- Adverse events [ Time Frame: At the end of each chemotherapy cycle, approximately every 21 days and 30 days after the final dose of chemotherapy ]
- Quality of Life [ Time Frame: Every 6 months through 36 months ]
- Post chemotherapy amenorrhea [ Time Frame: Assessed at randomization, prior to each cycle of chemotherapy, and every 6 months through 36 months for all pre-menopausal patients ]
- Change in LVEF at the 12-month evaluation [ Time Frame: Assessment at randomization and 12 months for first 1,120 patients enrolled ]
- HER-2 and Topo II gene amplification [ Time Frame: 6 years ]
- Recurrence-free interval [ Time Frame: Time from randomization to first local, regional, or distant recurrence ]
- Distant recurrence-free interval [ Time Frame: Time from randomization to distant disease recurrence ]
|Study Start Date:||May 2004|
|Study Completion Date:||May 2016|
|Primary Completion Date:||March 2014 (Final data collection date for primary outcome measure)|
Active Comparator: Arm 1: adriamycin + cyclophosphamide
Patients receive adriamycin IV over 15 minutes followed by cyclophosphamide IV over 30 minutes on day 1. Treatment repeats every 21 days for 4 courses.
Arm 1: cyclophosphamide 600 mg/m2 IV every 21 days for 4 cycles; Arm 2: cyclophosphamide 500 mg/m2 IV every 21 days for 6 cyclesDrug: adriamycin
adriamycin 60 mg/m2 IV every 21 days for 4 cycles
Experimental: Arm 2: fluorouracil + epirubicin + cyclophosphamide
Patients receive fluorouracil IV, epirubicin IV over 15 minutes, and cyclophosphamide IV over 30 minutes on day 1. Treatment repeats every 21 days for 6 courses.
Arm 1: cyclophosphamide 600 mg/m2 IV every 21 days for 4 cycles; Arm 2: cyclophosphamide 500 mg/m2 IV every 21 days for 6 cyclesDrug: epirubicin
epirubicin 100 mg/m2 IV every 21 days for 6 cycles
Other Name: epirubicin hydrochlorideDrug: fluorouracil
fluorouracil 500 mg/m2 IV every 21 days for 6 cycles
- Compare disease-free survival of women with node-negative breast cancer treated with adjuvant fluorouracil, epirubicin, and cyclophosphamide vs doxorubicin and cyclophosphamide.
- Compare survival, recurrence-free interval, and distant recurrence-free interval in patients treated with these regimens.
- Compare adverse events in patients treated with these regimens.
- Compare quality of life, with regard to physical functioning, vitality, symptoms, and rates of post-chemotherapy amenorrhea, in premenopausal patients treated with these regimens.
- Determine the effect of induction of post-chemotherapy amenorrhea on disease-free survival in premenopausal patients treated with these regimens.
- Correlate post-chemotherapy amenorrhea and disease-free survival with hormone receptor status in premenopausal patients treated with these regimens.
- Correlate changes in left ventricular ejection fraction (LVEF) with self-reported physical functioning in patients treated with these regimens.
- Compare the efficacy of these regimens in patients with Human Epidermal Growth Factor Receptor 2 (HER2)/neu and/or topoisomerase-2-alpha gene amplification.
OUTLINE: This is a randomized, multicenter study. Patients are stratified according to hormone receptor status (estrogen receptor [ER] positive or progesterone receptor [PR] positive vs ER negative or PR negative) and type of prior surgery (lumpectomy vs total mastectomy). Patients are randomized to 1 of 2 treatment arms.
- Arm 1: Patients receive doxorubicin IV over 15 minutes followed by cyclophosphamide IV over 30 minutes on day 1. Treatment repeats every 21 days for 4 courses.
- Arm 2: Patients receive fluorouracil IV, epirubicin IV over 15 minutes, and cyclophosphamide IV over 30 minutes on day 1. Treatment repeats every 21 days for 6 courses.
In both arms, treatment continues in the absence of disease progression or unacceptable toxicity.
All patients with ER- or PR-positive tumors receive hormonal therapy daily beginning within 3-12 weeks after the completion of chemotherapy and continuing for at least 5 years.
All patients who have undergone prior lumpectomy undergo whole-breast radiotherapy beginning as soon as possible after the completion of chemotherapy. Patients who have undergone prior total mastectomy may undergo chest wall radiotherapy at the investigator's discretion. Patients assigned to the partial breast irradiation (PBI) group of protocol NSABP-B-39 undergo PBI according to protocol-specific guidelines.
Quality of life is assessed at baseline, on day 1 of course 4 of chemotherapy, and then every 6 months for 3 years.
Patients are followed every 6 months for up to 5 years and then annually thereafter.
PROJECTED ACCRUAL: A total of 2,700 patients (1,350 per treatment arm) will be accrued for this study within 3.75 years.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00087178
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|Principal Investigator:||Norman Wolmark, MD||NSABP Foundation Inc|