Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Related Publications
Trial Contact Information

Alternate Title

Paclitaxel and Combination Chemotherapy in Treating Patients With Stage II or Stage III Breast Cancer

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase III	Treatment	Closed	18 to 78	NCI	NSABP-B-28

Objectives

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.

Entry Criteria

Disease Characteristics:

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

Prior/Concurrent Therapy:

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)

Patient Characteristics:

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

Expected Enrollment

This study will accrue 3050 patients over 21 months.

Outline

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.

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

Terry Mamounas, MD, MPH, FACS, Protocol chair		Ph: 330-363-6281 Email: tmamounas@aultman.com