Phase III Comparison of Preoperative vs Postoperative FEC (Fluorouracil/Epirubicin/Cyclophosphamide) in Women with Operable Breast Cancer
Combination Chemotherapy Before or After Surgery in Treating Women With Breast Cancer
Basic Trial Information
|Phase III||Treatment||Closed||16 to 70||EORTC-10902|
I. Determine whether 4 courses of preoperative chemotherapy with FEC (fluorouracil/epirubicin/cyclophosphamide) in women with operable breast cancer reduce the tumor size sufficiently to permit breast-conserving surgery in patients for whom mastectomy is initially planned. II. Compare disease-free and overall survival of women with operable breast cancer randomly assigned to 4 courses of FEC administered preoperatively vs. postoperatively (beginning within 36 hours of surgery). III. Evaluate the response of the primary tumor to preoperative chemotherapy and determine the correlation between this response and disease-free and overall survival.
Palpable, operable breast cancer that has been diagnosed by core needle biopsy (mandatory for T1c tumors) or fine needle aspiration within 21 days prior to entry Stage T1c-4b, N0-1, M0 Hormone receptor status: Not specified No bilateral breast cancer
No previous treatment for breast cancer Biologic therapy: Not specified Chemotherapy: No previous chemotherapy Endocrine therapy: Not specified Radiotherapy: Not specified Surgery: Core needle biopsy or fine needle aspiration within 21 days prior to entry Repeated core needle biopsy permitted
Age: 16 to 70 Sex: Women only Menopausal status: Not specified Performance status: WHO 0-2 Hematopoietic: WBC at least 4,000 Platelets at least 100,000 Hepatic: Bilirubin no greater than 2.8 mg/dL (50 micromoles/L) Renal: Creatinine no greater than 1.3 mg/dL (120 micromoles/L) Cardiovascular: No congestive heart failure No significant arrhythmia No bilateral bundle branch block No recent myocardial infarction No uncontrolled hypertension (diastolic pressure greater than 110 mm Hg) Other: No male breast cancer No pregnant or nursing women No second malignancy except adequately treated: Nonmelanomatous skin cancer Cervical cancer
1,100 evaluable patients will be entered on each treatment arm over approximately 4 years.
This is a randomized study. Patients are stratified by participating institution, clinical tumor size, clinical nodal status, age, and planned surgical treatment. The first group receives fluorouracil, epirubicin, and cyclophosphamide (FEC) every 3 weeks for a total of 4 courses, followed 3 weeks later by surgery. Radiotherapy for patients who undergo less than a mastectomy begins 2-4 weeks after completion of chemotherapy The second group undergoes breast-conserving surgery followed, within 24-36 hours, by chemotherapy with FEC as above. Radiotherapy for patients who undergo less than a mastectomy begins after surgery. All patients aged 50 years and older are given oral tamoxifen daily for at least 2 years, beginning 15 weeks after initiation of therapy. Patients are followed every 4 months for 2 years, every 6 months for up to 5 years, and annually thereafter.
van Nes JG, Putter H, Julien JP, et al.: Preoperative chemotherapy is safe in early breast cancer, even after 10 years of follow-up; clinical and translational results from the EORTC trial 10902. Breast Cancer Res Treat 115 (1): 101-13, 2009.[PUBMED Abstract]
Mieog JS, van der Hage JA, van de Vijuer MJ, et al.: Tumour response to preoperative anthracycline-based chemotherapy in operable breast cancer: the predictive role of p53 expression. Eur J Cancer 42 (10): 1369-79, 2006.[PUBMED Abstract]
van der Hage JA, van de Velde CJ, Julien JP, et al.: Preoperative chemotherapy in primary operable breast cancer: results from the European Organization for Research and Treatment of Cancer trial 10902. J Clin Oncol 19 (22): 4224-37, 2001.[PUBMED Abstract]
Tanis E, van de Velde CJ, Bartelink H, et al.: Locoregional recurrence after breast-conserving therapy remains an independent prognostic factor even after an event free interval of 10 years in early stage breast cancer. Eur J Cancer 48 (12): 1751-6, 2012.[PUBMED Abstract]
van der Hage JA, Mieog JS, van de Velde CJ, et al.: Impact of established prognostic factors and molecular subtype in very young breast cancer patients: pooled analysis of four EORTC randomized controlled trials. Breast Cancer Res 13 (3): R68, 2011.[PUBMED Abstract]
de Bock GH, Putter H, Bonnema J, et al.: The impact of loco-regional recurrences on metastatic progression in early-stage breast cancer: a multistate model. Breast Cancer Res Treat 117 (2): 401-8, 2009.[PUBMED Abstract]
Van Nes JGH, Putter H, Bartelink H, et al.: A prognostic index for local recurrences in women with early breast cancer using European Organization for Research and Treatment of Cancer (EORTC) studies. [Abstract] Breast Cancer Res Treat 100 (Suppl 1): A-2021, S86-7, 2006.
de Bock GH, van der Hage JA, Putter H, et al.: Isolated loco-regional recurrence of breast cancer is more common in young patients and following breast conserving therapy: long-term results of European Organisation for Research and Treatment of Cancer studies. Eur J Cancer 42 (3): 351-6, 2006.[PUBMED Abstract]
Trial Contact Information
Trial Lead Organizations
European Organization for Research and Treatment of Cancer
Note: The purpose of most clinical trials listed in this database is to test new cancer treatments, or new methods of diagnosing, screening, or preventing cancer. Because all potentially harmful side effects are not known before a trial is conducted, dose and schedule modifications may be required for participants if they develop side effects from the treatment or test. The therapy or test described in this clinical trial is intended for use by clinical oncologists in carefully structured settings, and may not prove to be more effective than standard treatment. A responsible investigator associated with this clinical trial should be consulted before using this protocol.