Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Related Publications
Trial Contact Information
| Phase | Type | Status | Age | Sponsor | Protocol IDs |
|---|---|---|---|---|---|
| Phase III | Treatment | Completed | 18-75, pre- and postmenopausal | NCI | NSABP-B-22 MAOP-1389, NCOG-NSABP-B-22 |
Objectives
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).
Entry Criteria
Disease Characteristics:
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
Prior/Concurrent Therapy:
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
Patient 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
Expected Enrollment
2,160 patients will be entered over about 3 years; an additional 3 years will be required for follow-up.
Outline
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.Published Results
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.
Related PublicationsWapnir 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 Lead Organizations
National Surgical Adjuvant Breast and Bowel Project
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| Norman Wolmark, MD, Protocol chair | |
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Clinical Research Program - Northern California Cancer Center
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| Robert Carlson, MD, Protocol chair | |
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Mid-Atlantic Oncology Program
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| James Ahlgren, MD, Protocol chair | |
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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.
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