Phase III Randomized Comparison of Adjuvant Chemotherapy with AC (ADR/CTX) vs AC Plus Reinduction with Parenteral CMF (Intravenous CTX/MTX/5-FU) vs Conventional CMF in Patients with Totally Resected Breast Cancer with Positive Nodes
Basic Trial Information
|Phase III||Treatment||Completed||18 to 59||NCI||NSABP-B-15|
I. Compare the disease-free intervals and survival of patients under the age of 60 years with potentially curable carcinoma of the breast treated postoperatively with adjuvant chemotherapy: AC (adriamycin/cyclophosphamide) vs. AC plus reinduction with parenteral CMF (intravenous cyclophosphamide/methotrexate/5-fluorouracil) vs. conventional CMF (oral cyclophosphamide/methotrexate/5-fluorouracil). II. Compare the morbidity associated with these therapeutic regimens.
See General Eligibility Criteria
See General Eligibility Criteria
General Eligibility Criteria:
Women under the age of 60 years who have undergone either total mastectomy plus axillary dissection or segmental mastectomy plus axillary dissection (the latter group will receive postoperative radiotherapy on protocol) for potentially curable carcinoma of the breast, provided they begin treatment 2-4 weeks postoperatively. Patients aged 50-59 years must have a progesterone receptor level of less than 10 fmol/mg cytosol protein, regardless of ER levels; specific receptor levels are not a condition for entry of patients aged 49 years and younger. Prior to entry, receptor levels must be determined for all patients by a laboratory that complies with NSABP quality control requirements. Patients who have undergone segmental mastectomy must not have had breast irradiation prior to entry. The tumor must be confined to the breast or the breast and ipsilateral axilla on clinical examination, movable in relation to the underlying muscle and chest wall, and movable with respect to the overlying skin; it must be invasive histologically, and there must be histologic evidence of tumor in at least one axillary lymph node. The axillary nodes must be movable in relation to the chest wall and neurovascular bundle and be no greater than 2 cm in size; there may be no edema of the arm. The life expectancy exclusive of cancer must be at least 10 years, and there must be adequate hematopoietic, renal, and hepatic function. Patients with skeletal pain are eligible only if the bone scan and/or x-ray examination reveals no evidence of metastatic disease. Patients with previous surgical oophorectomy are eligible if the oophorectomy was not performed for malignancy; patients may not have had radiation castration. Patients may not have breast malignancy other than carcinoma and may not have inflammatory carcinoma. Any mass in the contralateral breast must be demonstrated by biopsy to be benign. There may be no ulceration, erythema, skin infiltration, or peau d'orange of any magnitude, although patients with tethering or dimpling of the skin or nipple inversion are eligible. Palpable nodes in the contralateral axilla or in the supraclavicular or infraclavicular areas must be confirmed by biopsy as benign. Mastectomy must have taken place within 4 weeks of histologic diagnosis. There may be no previous or concomitant second malignancy except for effectively treated squamous or basal cell skin carcinoma or surgically treated carcinoma in situ of the cervix. There may have been no prior therapy for breast cancer other than mastectomy; hormonal therapy (e.g., birth control medication, replacement therapy, etc.) must be discontinued while on protocol. There must be no nonmalignant systemic disease that would preclude any of the therapeutic options; specifically, there may be no active cardiac disease that would contraindicate the use of adriamycin, including any documented myocardial infarction, angina pectoris that requires medication, history of CHF, valvular disease with documented compromise of cardiac function, cardiomegaly on chest x-ray, ventricular hypertrophy by EKG, or poorly controlled hypertension. Patients who have undergone segmental mastectomy must have had a tumor that was not greater than 4 cm in its largest dimension, must not have had removal of the nipple, must have had a breast small enough to permit satisfactory radiotherapy, and must have had a breast large enough to permit a cosmetically acceptable resection.
800 patients will be entered over about 2 years.
Randomized study. Patients are randomized to Arms I, II, and III. All patients who had segmental mastectomy receive Radiotherapy. Arm I: 2-Drug Combination Chemotherapy. AC: Adriamycin, ADR, NSC-123127; Cyclophosphamide, CTX, NSC-26271. Arm II: 2-Drug Combination Chemotherapy followed by Reinduction with 3-Drug Combination Chemotherapy. AC; followed by Parenteral CMF: Intravenous CTX; Methotrexate, MTX, NSC-740; 5-Fluorouracil, 5-FU, NSC-19893. Arm III: 3-Drug Combination Chemotherapy. Conventional CMF. Radiotherapy. Irradiation of the involved breast using Co60 or linear accelerators.
Paik S, Bryant J, Tan-Chiu E, et al.: HER2 and choice of adjuvant chemotherapy for invasive breast cancer: National Surgical Adjuvant Breast and Bowel Project Protocol B-15. J Natl Cancer Inst 92 (24): 1991-8, 2000.[PUBMED Abstract]
Fisher B, Brown AM, Dimitrov NV, et al.: Two months of doxorubicin-cyclophosphamide with and without interval reinduction therapy compared with 6 months of cyclophosphamide, methotrexate, and fluorouracil in positive-node breast cancer patients with tamoxifen-nonresponsive tumors: results from the National Surgical Adjuvant Breast and Bowel Project B-15. J Clin Oncol 8 (9): 1483-96, 1990.[PUBMED Abstract]
Gennari A, Sormani MP, Puntoni M, et al.: A pooled analysis on the interaction between HER-2 expression and responsiveness of breast cancer to adjuvant chemotherapy. [Abstract] Breast Cancer Res Treat 100 (Suppl 1): A-41, S19, 2006.
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]
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.