Clinical trial NCT00087178
Conditions: Breast Cancer
Keywords: stage I breast cancer stage II breast cancer
Sponsor: NSABP Foundation Inc
Start date: 2004-05-01; Completion date: 2016-05-01
Enrollment: 2722 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
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.

Detailed description:
OBJECTIVES:

Primary

* Compare disease-free survival of women with node-negative breast cancer treated with adjuvant fluorouracil, epirubicin, and cyclophosphamide vs doxorubicin and cyclophosphamide.

Secondary

* 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.

Arms: arm 1: 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 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.
Interventions: intervention 1: cyclophosphamide intervention 2: adriamycin intervention 3: epirubicin intervention 4: fluorouracil
Intervention descriptions: intervention 1: 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 cycles intervention 2: adriamycin 60 mg/m2 IV every 21 days for 4 cycles intervention 3: epirubicin 100 mg/m2 IV every 21 days for 6 cycles intervention 4: fluorouracil 500 mg/m2 IV every 21 days for 6 cycles

Protocol documents: