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Clinical Trials (PDQ®)

  • Last Modified: 5/9/2006

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Clinical Trials (PDQ®)

Phase III Randomized Study of CTX Dose Intensification vs Increased Cumulative CTX Dose vs Standard Dose/Schedule AC (DOX/CTX) as Postoperative Adjuvant Therapy in Patients with Node-Positive Breast Cancer

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

Basic Trial Information

PhaseTypeStatusAgeSponsorProtocol IDs
Phase IIITreatmentCompleted18-75, pre- and postmenopausalNCINSABP-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 Publications

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]

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 Contact Information

Trial Lead Organizations

National Surgical Adjuvant Breast and Bowel Project

Norman Wolmark, MD, Protocol chair
Ph: 412-359-3336; 866-680-0004

Clinical Research Program - Northern California Cancer Center

Robert Carlson, MD, Protocol chair
Ph: 650-725-6457; 800-756-9000

Mid-Atlantic Oncology Program

James Ahlgren, MD, Protocol chair
Ph: 202-741-2478
Email: w4rx@alum.mit.edu

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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