Phase III Comparison of Adjuvant Sequential Chemotherapy with MTX/5-FU vs No Adjuvant Therapy in Patients with Negative Axillary Nodes Following Mastectomy for ER-Negative Breast Cancer
Basic Trial Information
|Phase III||Treatment||Completed||18 to 70||NCI||NSABP-B-13|
I. Compare disease-free interval and survival of patients with negative axillary nodes following mastectomy for ER-negative breast cancer who are randomly assigned to adjuvant sequential therapy with methotrexate followed by 5-fluorouracil vs. no adjuvant therapy. II. In conjunction with the results of NSAPB-B-14, evaluate whether treatment failure and survival correlate with ER level in post-mastectomy, negative-node patients who receive no further treatment. III. Evaluate the influence of both hormone receptor status and the interaction of radiotherapy and sequential methotrexate/5-fluorouracil chemotherapy on the rate of local breast recurrence in patients who have undergone segmental mastectomy and axillary node dissection for their disease.
See General Eligibility Criteria
See General Eligibility Criteria
General Eligibility Criteria:
Female patients under the age of 71 years who have undergone either total mastectomy and axillary dissection or segmental mastectomy and axillary dissection (to be followed by breast irradiation) for potentially curable carcinoma of the breast, provided all axillary nodes are proven histologically to be negative, the ER level of the tumor is less than 10 fmol/mg cytosol protein, and the PR level has been quantified. The interval between mastectomy and proposed randomization and treatment must not exceed 35 days, and no more than 4 weeks may have intervened between diagnosis and mastectomy. The tumor must be confined to the breast clinically, movable relative to the underlying muscle and chest wall, movable relative to the skin, and invasive on histological examination. There may be no ulceration, erythema, infiltration of the skin, peau d'orange, satellite breast nodules or parasternal nodules, or edema of the arm. Patients with inflammatory carcinoma and those with tumors other than carcinoma are excluded. If there are palpable ipsilateral or contralateral axillary nodes preoperatively or palpable supraclavicular or infraclavicular nodes, these must be demonstrated to be free of tumor histologically. Patients with bilateral breast cancer are excluded, as are those with a mass in the contralateral breast unless there is biopsy proof of nonmalignancy. Patients with bone pain may be entered only if a bone scan and/or x-ray examination reveals no metastatic disease. There may have been no prior therapy for breast cancer and no previous or concurrent second malignancy aside from effectively treated basal cell carcinoma of the skin and carcinoma in situ of the cervix that has been treated surgically only. Patients may have had a previous surgical oophorectomy for a nonmalignant condition, but radiation castration renders a patient ineligible. Adequate hematopoietic and hepatic function must be documented by the following: WBC at least 4,000 and platelets at least 100,000; and bilirubin not over 1.5 mg/dl and SGOT not over 60 IU/ml. Renal function must be adequate, and a 24-hour creatinine clearance must be performed postoperatively and the results available prior to randomization. There must be no nonmalignant systemic disease that would preclude any protocol treatment and no psychiatric or addictive disorder that would preclude obtaining informed consent. Pregnancy excludes. In addition to fulfilling the foregoing entry criteria, patients who undergo segmental resection must have a tumor that is no greater than 4 cm in greatest diameter on clinical examination and must have a breast of sufficient size to permit a cosmetically acceptable resection but not so large that satisfactory breast irradiation is not possible; the tumor must be so located that adequate resection can be accomplished without removal of the nipple. Candidates for segmental mastectomy must not have diffuse tumor demonstrated on xeroradiography or mammography and must not have more than one tumor in the same breast unless all but one is histologically proven to be benign. Radiotherapy must not have been given following segmental resection prior to randomization.
1,350-1,440 patients will be accrued in 4-5 years.
Randomized study. All patients are randomized on Arms I and II; segmental mastectomy patients are also treated on Regimen A. Arm I: 2-Drug Sequential Combination Chemotherapy plus Leucovorin Rescue. Methotrexate, MTX, NSC-740; 5-Fluorouracil, 5-FU, NSC-19893; Citrovorum Factor, Leucovorin, CF, NSC-3590. Arm II: No further treatment. Regimen A: Radiotherapy. Breast irradiation using Co60 or linear accelerator x-rays.
Fisher B, Dignam J, Mamounas EP, et al.: Sequential methotrexate and fluorouracil for the treatment of node-negative breast cancer patients with estrogen receptor-negative tumors: eight-year results from National Surgical Adjuvant Breast and Bowel Project (NSABP) B-13 and first report of findings from NSABP B-19 comparing methotrexate and fluorouracil with conventional cyclophosphamide, methotrexate, and fluorouracil. J Clin Oncol 14 (7): 1982-92, 1996.[PUBMED Abstract]
Fisher B, Costantino J, Wickerham L, et al.: Adjuvant therapy for node-negative breast cancer: an update of NSABP findings. [Abstract] Proceedings of the American Society of Clinical Oncology 12: A-79, 69, 1993.
Fisher B, Redmond C, Dimitrov NV, et al.: A randomized clinical trial evaluating sequential methotrexate and fluorouracil in the treatment of patients with node-negative breast cancer who have estrogen-receptor-negative tumors. N Engl J Med 320 (8): 473-8, 1989.[PUBMED Abstract]
Fisher B, Redmond C, Wickerham DL, et al.: Systemic therapy in patients with node-negative breast cancer. A commentary based on two National Surgical Adjuvant Breast and Bowel Project (NSABP) clinical trials. Ann Intern Med 111 (9): 703-12, 1989.[PUBMED Abstract]
Anderson SJ, Wapnir I, Dignam JJ, et al.: Prognosis after ipsilateral breast tumor recurrence and locoregional recurrences in patients treated by breast-conserving therapy in five national surgical adjuvant breast and bowel project protocols of node-negative breast cancer. J Clin Oncol 27 (15): 2466-73, 2009.[PUBMED Abstract]
Taghian AG, Jeong JH, Mamounas EP, et al.: Low locoregional recurrence rate among node-negative breast cancer patients with tumors 5 cm or larger treated by mastectomy, with or without adjuvant systemic therapy and without radiotherapy: results from five national surgical adjuvant breast and bowel project randomized clinical trials. J Clin Oncol 24 (24): 3927-32, 2006.[PUBMED Abstract]
Fisher B, Jeong JH, Anderson S, et al.: Treatment of axillary lymph node-negative, estrogen receptor-negative breast cancer: updated findings from National Surgical Adjuvant Breast and Bowel Project clinical trials. J Natl Cancer Inst 96 (24): 1823-31, 2004.[PUBMED Abstract]
Fisher B, Dignam J, Tan-Chiu E, et al.: Prognosis and treatment of patients with breast tumors of one centimeter or less and negative axillary lymph nodes. J Natl Cancer Inst 93 (2): 112-20, 2001.[PUBMED Abstract]
Fisher B, Jeong JH, Dignam J, et al.: Findings from recent National Surgical Adjuvant Breast and Bowel Project adjuvant studies in stage I breast cancer. J Natl Cancer Inst Monogr (30): 62-6, 2001.[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.
Fisher ER, Kenny JP, Sass R, et al.: Medullary cancer of the breast revisited. Breast Cancer Res Treat 16 (3): 215-29, 1990.[PUBMED Abstract]
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.