Phase III Randomized Study of Paclitaxel vs No Further Chemotherapy Following Doxorubicin/Cyclophosphamide for Resected Node-Positive Breast Cancer
Paclitaxel and Combination Chemotherapy in Treating Patients With Stage II or Stage III Breast Cancer
Basic Trial Information
|Phase III||Treatment||Closed||18 to 78||NCI||NSABP-B-28|
I. Compare disease-free survival and overall survival of patients with resected node-positive breast cancer treated with 4 courses of paclitaxel following 4 courses of doxorubicin/cyclophosphamide (AC) vs. 4 courses of AC alone.
Completely resected breast cancer Clinically confined to 1 breast and ipsilateral nodes (T1-3, N0-1, M0) Bone scan and/or x-rays negative for metastases in presence of bone pain X-ray, magnetic resonance imaging, or biopsy confirmation required for suspicious lesions Total mastectomy/lumpectomy and axillary node dissection required Histologic confirmation of invasive adenocarcinoma At least 1 involved axillary lymph node Additional criteria for lumpectomy: Primary tumor no greater than 5 cm on physical exam No invasive tumor or ductal carcinoma in situ in resection margins Re-excision permitted to obtain clear margins Total mastectomy required if clear margins unobtainable No diffuse tumors on mammogram unless surgically amenable to lumpectomy No ipsilateral mass following lumpectomy unless histologically benign No breast irradiation prior to randomization None of the following: Contralateral breast cancer Biopsy required for: Suspicious mass in breast Suspicious palpable axillary node Palpable supraclavicular or infraclavicular node Ulceration Erythema Infiltration of skin or underlying chest wall Tethering or dimpling of skin, or nipple inversion only, allowed Peau d'orange or skin edema of any magnitude Hormone receptor status: Estrogen and progesterone receptor status required prior to randomization Randomization within 63 days of initial cytologic or histologic diagnosis
No prior therapy for breast cancer other than surgery Segmental resection of ipsilateral or contralateral lobular carcinoma in situ allowed No prior anthracycline for any malignancy No concurrent sex hormone therapy (e.g., birth control pills, ovarian hormone replacement therapy)
Age: 18 to 78 Sex: Not specified Menopausal status: Not specified Performance status: Not specified Life expectancy: At least 10 years Hematopoietic: (at time of randomization) WBC at least 4,000/mm3 Platelet count at least 100,000/mm3 Hepatic: (at time of randomization) Bilirubin normal AST or ALT normal Renal: (at time of randomization) Creatinine normal Cardiovascular: No contraindication to doxorubicin or paclitaxel therapy, including: Myocardial infarction Angina pectoris requiring medication History of documented congestive heart failure Arrhythmia requiring medication Severe conduction abnormality Valvular disease with documented cardiac function compromise Cardiomegaly on chest x-ray or ventricular hypertrophy on EKG unless left ventricular ejection fraction at least 45% on MUGA or echocardiogram Poorly controlled hypertension, i.e., diastolic above 100 mm Hg Concurrent medication that alters cardiac conduction (e.g., digitalis, beta- blockers, calcium channel blockers) allowed for hypertension or noncardiac condition Other: No nonmalignant systemic disease that precludes treatment or follow-up No psychiatric or addictive disorder that precludes informed consent No second malignancy within 10 years except: Effectively treated nonmelanomatous skin cancer Surgically treated carcinoma in situ of the cervix No pregnant women Chest x-ray within 3 months prior to randomization Bilateral mammogram, bone scan, EKG, and gynecologic exam within 1 year prior to randomization
This study will accrue 3050 patients over 21 months.
This is a randomized study. Patients are stratified on the basis of number of positive nodes, tamoxifen assignment (based on age and hormone-receptor status), type of surgery, and participating institution. Randomization must occur within 63 days of initial diagnosis, and treatment begins no sooner than 2 weeks after the last surgery. Patients in the first group receive doxorubicin and cyclophosphamide (AC) every 21 days for 4 courses. Patients in the second group receive paclitaxel every 21 days for 4 courses following completion of AC as in the first group. All patients over 50 years of age or with hormone-receptor-positive tumors receive oral daily tamoxifen for 5 years, beginning concurrently with chemotherapy. Patients who underwent lumpectomy receive radiotherapy upon completion of their chemotherapy. Granulocyte colony-stimulating factor is prohibited except to treat life-threatening infection, febrile neutropenia, or prolonged granulocytopenia. Hormonal therapy other than tamoxifen is prohibited on study. Patients are followed every 6 months for 2.5 years, then yearly.
Pusztai L, Jeong JH, Gong Y, et al.: Evaluation of microtubule-associated protein-Tau expression as a prognostic and predictive marker in the NSABP-B 28 randomized clinical trial. J Clin Oncol 27 (26): 4287-92, 2009.[PUBMED Abstract]
Yang SX, Costantino JP, Nguyen D, et al.: Correlation of levels of Akt phosphorylation at Ser473 with benefit from paclitaxel chemotherapy in NSABP B-28 patients with node-positive breast cancer. [Abstract] J Clin Oncol 27 (Suppl 15): A-537, 2009.
Mamounas EP, Bryant J, Lembersky B, et al.: Paclitaxel after doxorubicin plus cyclophosphamide as adjuvant chemotherapy for node-positive breast cancer: results from NSABP B-28. J Clin Oncol 23 (16): 3686-96, 2005.[PUBMED Abstract]
Mamounas EP, Bryant J, Lembersky BC, et al.: Paclitaxel (T) following doxorubicin/cyclophosphamide (AC) as adjuvant chemotherapy for node-positive breast cancer: results from NSABP B-28. [Abstract] Proceedings of the American Society of Clinical Oncology 22: A-12, 4, 2003.
Soran A, Nesbitt L, Mamounas EP, et al.: Centralized medical monitoring in phase III clinical trials: the National Surgical Adjuvant Breast and Bowel Project (NSABP) experience. Clin Trials 3 (5): 478-85, 2006.[PUBMED Abstract]
Campone M, Fumoleau P, Bourbouloux E, et al.: Taxanes in adjuvant breast cancer setting: which standard in Europe? Crit Rev Oncol Hematol 55 (3): 167-75, 2005.[PUBMED Abstract]
Piccart MJ, Lohrisch C, Duchateau L, et al.: Taxanes in the adjuvant treatment of breast cancer: why not yet? J Natl Cancer Inst Monogr (30): 88-95, 2001.[PUBMED Abstract]
Trial Contact Information
Trial Lead Organizations
National Surgical Adjuvant Breast and Bowel Project
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.