NCI HIGH PRIORITY CLINICAL TRIAL --- Phase III Comparison of Preoperative vs Postoperative Short-Term Intensive Combination Chemotherapy with AC (DOX/CTX) in Women with Resectable Carcinoma of the Breast
Basic Trial Information
|Phase III||Treatment||Completed||18-75, pre/postmenopausal||NCI||NSABP-B-18|
I. Compare disease-free survival and overall survival among patients with operable carcinoma of the breast randomly assigned to four courses of preoperative vs. postoperative combination chemotherapy with AC (doxorubicin/cyclophosphamide). II. Evaluate the response of the primary tumor to preoperative chemotherapy, and correlate the response with disease-free survival and survival. III. Determine whether reduction in the size of the primary tumor by preoperative chemotherapy will permit more conservative surgery and decrease the incidence of recurrence in the ipsilateral breast.
Breast cancer with tumor palpable on clinical examination (T1-3) and confined to the breast or breast and ipsilateral axilla Diagnosis made on tissue obtained by fine needle aspiration cytology (preferred) or by core biopsy but not by incisional or excisional biopsy Tumor must be movable in relation to overlying skin and underlying muscle and chest wall on clinical examination Palpable axillary nodes must be movable in relation to each other and to chest wall and neurovascular bundle Nodes may be of any size but must not be associated with edema of the arm No ulceration, erythema, complete fixation to the skin, peau d'orange of any degree, satellite breast nodules, or parasternal nodules Tethering or dimpling of skin or nipple inversion allowed No cancer in the contralateral breast Patients with a mass in the opposite breast and those with palpable nodes in the contralateral axilla or in the supraclavicular or infraclavicular areas must have biopsy proof that there is no malignancy in these areas No bone pain unless bone scan and/or x-ray rules out metastatic disease Interval between initial diagnosis and randomization may not exceed 56 days Hormone receptor status: Not required prior to randomization
Biologic therapy: No prior immunotherapy for breast cancer Chemotherapy: No prior chemotherapy for breast cancer Endocrine therapy: No prior hormonal therapy for breast cancer Sex hormone therapy other than that stipulated on protocol (e.g., birth control pills, ovarian replacement hormonal therapy) must be discontinued for duration of protocol treatment Radiotherapy: No prior radiotherapy for breast cancer No prior radiation castration Surgery: No prior surgery Prior surgical oophorectomy for reasons other than malignancy allowed
Age: 18 to 75 Sex: Women only Menopausal status: Pre- or postmenopausal Performance status: Not specified Life expectancy: At least 10 years exclusive of breast cancer Hematopoietic: WBC at least 4,000 Platelets at least 100,000 Hepatic: Bilirubin no greater than 1.5 mg/dl SGOT no greater than 60 IU/ml No hepatic disease that would preclude protocol therapy Renal: Creatinine no greater than 1.5 mg/dl No renal disease that would preclude protocol therapy Cardiovascular: No contraindication to the use of doxorubicin, i.e.: No documented MI No angina pectoris requiring medication No history of CHF No cardiac arrhythmia associated with cardiac dysfunction No valvular disease with documented compromise in cardiac function No cardiomegaly on x-ray No poorly controlled hypertension (diastolic pressure greater than 100 mm Hg) Other: No other nonmalignant systemic disease that would preclude protocol therapy No pregnancy at randomization No previous or concomitant malignancy except: Effectively treated nonmelanomatous skin cancer Surgically treated in situ cervical or uterine carcinoma No psychiatric or addictive disorder that precludes informed consent
A total of 1,510 patients will be entered.
Randomized study. All patients are randomized on Arms I and II. All patients aged 50 years and older at the time of randomization receive antiestrogen therapy with tamoxifen (Regimen A) following chemotherapy on either arm. Patients on either arm whose surgical procedure is a segmental mastectomy receive postoperative radiotherapy on Regimen B. Arm I: Surgery followed by 2-Drug Combination Chemotherapy. Radical or segmental mastectomy and axillary dissection; followed by AC: Doxorubicin, DOX, NSC-123127; Cyclophosphamide, CTX, NSC-26271. Arm II: 2-Drug Combination Chemotherapy followed by Surgery. AC; followed by radical or segmental mastectomy and axillary dissection. Regimen A: Antiestrogen Therapy. Tamoxifen, TMX, NSC-180973. Regimen B: Radiotherapy. Irradiation of the remaining breast tissue (equipment not specified).
Mamounas EP, Wang J, Bryant J, et al.: Patterns of loco-regional failure (LRF) in patients receiving neoadjuvant chemotherapy (NC): results from NSABP B-18. [Abstract] Breast Cancer Res Treat 82 (Suppl 1): A-35, S17, 2003.
Fisher ER, Wang J, Bryant J, et al.: Pathobiology of preoperative chemotherapy: findings from the National Surgical Adjuvant Breast and Bowel (NSABP) protocol B-18. Cancer 95 (4): 681-95, 2002.[PUBMED Abstract]
Wolmark N, Wang J, Mamounas E, et al.: Preoperative chemotherapy in patients with operable breast cancer: nine-year results from National Surgical Adjuvant Breast and Bowel Project B-18. J Natl Cancer Inst Monogr (30): 96-102, 2001.[PUBMED Abstract]
Fisher B, Bryant J, Wolmark N, et al.: Effect of preoperative chemotherapy on the outcome of women with operable breast cancer. J Clin Oncol 16 (8): 2672-85, 1998.[PUBMED Abstract]
Fisher B, Brown A, Mamounas E, et al.: Effect of preoperative therapy for primary breast (BC) on local-regional disease, disease-free survival (DFS) and survival (S) : results from NSABP B-18. [Abstract] Proceedings of the American Society of Clinical Oncology 16: A-449, 1997.
Fisher B, Brown A, Mamounas E, et al.: Effect of preoperative chemotherapy on local-regional disease in women with operable breast cancer: findings from National Surgical Adjuvant Breast and Bowel Project B-18. J Clin Oncol 15 (7): 2483-93, 1997.[PUBMED Abstract]
Fisher B, Rockette H, Robidoux A, et al.: Effect of preoperative therapy for breast cancer (BC) on local-regional disease: first report of NSABP B-18. [Abstract] Proceedings of the American Society of Clinical Oncology 13: A-57, 64, 1994.
Mamounas EP, Anderson SJ, Dignam JJ, et al.: Predictors of locoregional recurrence after neoadjuvant chemotherapy: results from combined analysis of National Surgical Adjuvant Breast and Bowel Project B-18 and B-27. J Clin Oncol 30 (32): 3960-6, 2012.[PUBMED Abstract]
Rastogi P, Anderson SJ, Bear HD, et al.: Preoperative chemotherapy: updates of National Surgical Adjuvant Breast and Bowel Project Protocols B-18 and B-27. J Clin Oncol 26 (5): 778-85, 2008.[PUBMED Abstract]
Wapnir IL, Anderson SJ, Mamounas EP, et al.: Prognosis after ipsilateral breast tumor recurrence and locoregional recurrences in five National Surgical Adjuvant Breast and Bowel Project node-positive adjuvant breast cancer trials. J Clin Oncol 24 (13): 2028-37, 2006.[PUBMED Abstract]
Swain SM, Wilson JW, Mamounas EP, et al.: Estrogen receptor status of primary breast cancer is predictive of estrogen receptor status of contralateral breast cancer. J Natl Cancer Inst 96 (7): 516-23, 2004.[PUBMED Abstract]
Taghian A, Jeong JH, Mamounas E, et al.: Patterns of locoregional failure in patients with operable breast cancer treated by mastectomy and adjuvant chemotherapy with or without tamoxifen and without radiotherapy: results from five National Surgical Adjuvant Breast and Bowel Project randomized clinical trials. J Clin Oncol 22 (21): 4247-54, 2004.[PUBMED Abstract]
Mamounas EP, Fisher B: Preoperative (neoadjuvant) chemotherapy in patients with breast cancer. Semin Oncol 28 (4): 389-99, 2001.[PUBMED Abstract]
Mamounas EP, Fisher B: Preoperative chemotherapy for operable breast cancer. Cancer Treat Res 103: 137-55, 2000.[PUBMED Abstract]
McCaskill-Stevens W, Bryant J, Costantino J, et al.: Incidence of contralateral breast cancer (CBC), endometrial cancer (EC), and thromboembolic events (TE) in African American (AA) women receiving tamoxifen for treatment of primary breast cancer. [Abstract] Proceedings of the American Society of Clinical Oncology 19: A269, 2000.
Trial Contact Information
Trial Lead Organizations
National Surgical Adjuvant Breast and Bowel Project
Ph: 412-359-3336; 866-680-0004
Clinical Research Program - Northern California Cancer Center
Ph: 650-725-6457; 800-756-9000
Mid-Atlantic Oncology Program
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.