Phase III Randomized Comparison of Adjuvant Chemohormonal Therapy with ACT (DOX/CTX/TMX) vs PAFT (L-PAM/DOX/5-FU/TMX) vs TMX Alone in Patients Aged 50 Years and Older with Potentially Curable Breast Carcinoma
Basic Trial Information
|Phase III||Treatment||Completed||over 50||NCI||NSABP-B-16|
I. Compare the failure rates in patients aged of 50-70 years with potentially curable carcinoma of the breast treated postoperatively with ACT (doxorubicin/cyclophosphamide/tamoxifen) vs. PAFT (melphalan/doxorubicin/fluorouracil/tamoxifen) vs. tamoxifen alone.
Histologically proven invasive carcinoma of the breast definitively removed by either: Total mastectomy with axillary node dissection Segmental mastectomy with axillary node dissection No more than 35 days between mastectomy and randomization, with radiotherapy planned on study for patients who underwent segmental mastectomy No more than 4 weeks between diagnosis and mastectomy Histology established by excisional, incisional, or needle biopsy and aspiration cytology Tumor clinically confined to the breast or breast and ipsilateral axilla and movable relative to the underlying muscle, chest wall, and skin Histologic proof of ipsilateral axillary node involvement required Involved nodes clinically must be movable in relation to each other, the chest wall, and the neurovascular bundle Nodes no greater than 2 cm in largest diameter Palpable contralateral axillary nodes or palpable supraclavicular or infraclavicular nodes must be biopsy-proven benign Hormone receptor status: PgR at least 10 fmol/mg (any ER level) and age 50-59 Any ER/PgR status and age 60 or over Quantitative receptor data must be available prior to randomization The following exclude: Ulceration Erythema Infiltration of the skin Peau d'orange or any degree of skin edema Satellite breast nodules Parasternal nodules Edema of the arm Infiltration of the skin Tethering, skin dimpling, and nipple inversion are not to be interpreted as skin infiltration and patients with these conditions are eligible Inflammatory carcinoma Histologies other than carcinoma Bilateral breast cancer Any mass in the contralateral breast must be biopsy- proven benign Metastatic disease Patients with bone pain with negative bone scan and/or x-rays are eligible Segmental mastectomy patients must additionally meet the following criteria: Tumor clinically no greater than 5 cm in greatest diameter Mammography preferred No more than 1 malignant mass in the breast Other masses must be biopsy-proven benign Breast is of a size to allow a cosmetically acceptable resection Breast sufficiently small to permit satisfactory irradiation No breast irradiation 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 No prior oophorectomy for malignancy (oophorectomy for other reasons allowed) No prior radiation castration Hormonal therapy other than that stipulated by protocol (e.g., birth control, replacement therapy) must be discontinued on entry Radiotherapy: No prior radiotherapy for breast cancer Surgery: See Disease Characteristics
Age: Over 50 Sex: Female only Menopausal status: Not specified Performance status: Not specified Life expectancy: At least 10 years exclusive of breast cancer Hematopoietic: (obtained postoperatively) WBC at least 4,000 Platelets at least 100,000 Hepatic: (obtained postoperatively) Bilirubin no greater than 1.5 mg/dl SGOT no greater than 60 IU/ml Renal: (obtained postoperatively) Creatinine no greater than 1.5 mg/dl Cardiovascular: No documented MI No angina pectoris requiring antianginal medication No documented history of CHF No arrhythmia associated with heart failure or dysfunction No valvular disease with documented cardiac function compromise No cardiomegaly on chest x-ray No ventricular hypertrophy on EKG No poorly controlled hypertension, i.e., diastolic pressure greater than 100 (hypertension well controlled on medication allowed) Other: No psychiatric or addictive disorder that would preclude informed consent No nonmalignant systemic disease that would preclude any protocol therapy or prolonged follow-up No second malignancy except: Curatively treated nonmelanomatous skin cancer In situ cervical cancer treated by surgery only No pregnancy
Accrual as of November, 1988, was 1,221 of a total accrual target of 1,400.
Randomized study. Patients are randomized to Arms I, II, and III. All patients who had segmental mastectomy receive radiotherapy on Regimen A. Arm I: Antiestrogen Therapy. Tamoxifen, TMX, NSC-180973. Arm II: 2-Drug Combination Chemotherapy plus Antiestrogen Therapy. ACT: Doxorubicin, DOX, NSC-123127; Cyclophosphamide, CTX, NSC-26271; plus TMX. Arm III: 3-Drug Combination Chemotherapy plus Antiestrogen Therapy. PAFT: Melphalan, L-PAM, NSC-8806; DOX; Fluorouracil, 5-FU, NSC-19893; plus TMX. Regimen A: Radiotherapy. Irradiation of the involved breast using Co60 or linear accelerators.
Fisher B, Redmond C, Legault-Poisson S, et al.: Postoperative chemotherapy and tamoxifen compared with tamoxifen alone in the treatment of positive-node breast cancer patients aged 50 years and older with tumors responsive to tamoxifen: results from the National Surgical Adjuvant Breast and Bowel Project B-16. J Clin Oncol 8 (6): 1005-18, 1990.[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]
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]
Wickerham L: Tamoxifen--an update on current data and where it can now be used. Breast Cancer Res Treat 75 (Suppl 1): S7-12; discussion S33-5, 2002.[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.
Wapnir I, Anderson S, Tan-Chiu E, et al.: Ipsilateral breast tumor recurrence (IBTR) and survival in NSABP node-positive breast cancer protocols. [Abstract] Proceedings of the American Society of Clinical Oncology 19: A315, 2000.
Trial Contact Information
Trial Lead Organizations
National Surgical Adjuvant Breast and Bowel Project
Ph: 412-359-3336; 866-680-0004
Mid-Atlantic Oncology Program
Clinical Research Program - Northern California Cancer Center
Ph: 650-725-6457; 800-756-9000
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.