Phase III Randomized Study of CTX Dose Intensification vs Increased Cumulative CTX Dose vs Standard Dose/Schedule AC (DOX/CTX) as Postoperative Adjuvant Therapy in Patients with Node-Positive Breast Cancer
Basic Trial Information
|Phase III||Treatment||Completed||18-75, pre- and postmenopausal||NCI||NSABP-B-22|
I. Compare disease-free survival and overall survival of axillary node-positive breast cancer patients randomized to postoperative adjuvant chemotherapy with standard dose/schedule doxorubicin/cyclophosphamide (AC) vs. AC with dose-intensive cyclophosphamide (larger but fewer doses, same cumulative dose) vs. AC with dose-intensive cyclophosphamide and increased cumulative cyclophosphamide (higher dose, standard duration).
Histologically proven invasive carcinoma of the breast definitively removed by either: Total mastectomy with axillary node dissection Lumpectomy with axillary node dissection No more than 35 days between mastectomy and randomization, with radiotherapy planned on study for patients who underwent lumpectomy No more than 28 days between histologic/cytologic 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: 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 Lumpectomy patients must additionally meet the following criteria: Tumor clinically no greater than 5 cm in greatest diameter No diffuse tumors on xeroradiography or mammography that would not be amenable to lumpectomy 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 Negative resection margins required 1 re-resection to obtain negative margins allowed if within 28 days of diagnosis Total mastectomy required if second resection fails to obtain negative margins 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: Pre- and postmenopausal 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 or SGPT 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
2,160 patients will be entered over about 3 years; an additional 3 years will be required for follow-up.
Randomized study. All patients 50 years of age and older begin antiestrogen therapy on Regimen A concomitantly with chemotherapy. Patients who enter following lumpectomy receive radiotherapy on Regimen B after completion of chemotherapy. Arm I: 2-Drug Combination Chemotherapy. AC: Doxorubicin, DOX, NSC-123127; Cyclophosphamide, CTX, NSC-26271. Standard dose and schedule. Arm II: 2-Drug Combination Chemotherapy. AC. Intensified individual CTX doses, same cumulative CTX dose. Arm III: 2-Drug Combination Chemotherapy. AC. Intensified individual CTX doses and increased cumulative CTX dose. Regimen A: Antiestrogen Therapy. Tamoxifen, TMX, NSC-180973. Regimen B: Radiotherapy. Irradiation of the whole breast using Co60 equipment or linear accelerator with a minimum energy of 4 MV.
Fisher B, Anderson S, Wickerham DL, et al.: Increased intensification and total dose of cyclophosphamide in a doxorubicin-cyclophosphamide regimen for the treatment of primary breast cancer: findings from National Surgical Adjuvant Breast and Bowel Project B-22. J Clin Oncol 15 (5): 1858-69, 1997.[PUBMED Abstract]
Dimitrov N, Anderson S, Fisher B, et al.: Dose intensification and increased total dose of adjuvant chemotherapy for breast cancer (BC): findings from NSABP B-22. [Abstract] Proceedings of the American Society of Clinical Oncology 13: A-58, 64, 1994.
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]
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
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.