RATIONALE: Drugs used in chemotherapy, such as doxorubicin, cyclophosphamide, and paclitaxel, use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug and giving them after surgery may kill any remaining tumor cells. It is not yet known which combination chemotherapy regimen is more effective in treating resected breast cancer.

PURPOSE: Randomized phase III trial to compare the effectiveness of four adjuvant chemotherapy regimens using doxorubicin, cyclophosphamide, and paclitaxel in treating patients who have undergone surgery for stage I, stage II, or stage III breast cancer.

Condition	Treatment or Intervention	Phase
stage I breast cancer stage II breast cancer stage IIIA breast cancer stage IIIC breast cancer Male Breast Cancer	Drug: cyclophosphamide  Drug: doxorubicin  Drug: filgrastim  Drug: paclitaxel  Drug: pegfilgrastim  Procedure: adjuvant therapy  Procedure: biological response modifier therapy  Procedure: chemotherapy  Procedure: colony-stimulating factor therapy  Procedure: cytokine therapy	Phase III

OBJECTIVES:

• Compare the disease-free survival of patients with node-positive or high-risk node-negative breast cancer treated with 4 different schedules of adjuvant doxorubicin, cyclophosphamide, and paclitaxel.
• Compare the overall survival of patients treated with these regimens.
• Compare the toxic effects of these regimens in these patients.
• Correlate outcome with putative prognostic markers in patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are randomized to 1 of 4 treatment arms.

• Patients receive doxorubicin IV and cyclophosphamide IV on day 1 and pegfilgrastim subcutaneously (SC) on day 2. Treatment repeats every 14 days for 6 courses. Beginning 2 weeks after completion of doxorubicin and cyclophosphamide, patients receive paclitaxel IV over 3 hours on day 1 and pegfilgrastim SC on day 2. Treatment repeats every 14 days for 6 courses.
• Patients receive doxorubicin IV on day 1, oral cyclophosphamide on days 1-7, and filgrastim (G-CSF) SC on days 2-7. Treatment repeats every 7 days for 15 courses. Beginning 2 weeks after completion of cyclophosphamide, patients receive paclitaxel and pegfilgrastim as in arm I.
• Patients receive doxorubicin, cyclophosphamide, and pegfilgrastim as in arm I. Beginning 2 weeks after completion of doxorubicin and cyclophosphamide, patients receive paclitaxel IV over 1 hour on day 1. Treatment repeats every 7 days for 12 courses.
• Patients receive doxorubicin, cyclophosphamide, and G-CSF as in arm II. Beginning 2 weeks after completion of cyclophosphamide, patients receive paclitaxel as in arm III.

In all arms, treatment continues in the absence of disease progression or unacceptable toxicity.

In all arms, patients with estrogen-receptor or progesterone-receptor positive tumors receive hormonal therapy beginning within 28 days of the completion of adjuvant chemotherapy or radiotherapy (if given).

Patients are followed every 6 months for 5 years and then annually for 15 years.

PROJECTED ACCRUAL: A total of 4,500 patients (1,125 per treatment arm) will be accrued for this study within 2.25 years.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed stage I-III invasive breast cancer
• Operable disease
• Stage I, II, IIIA, and IIIC (T1-3, N3a only)
• No T4 tumors
• High-risk disease, defined by 1 of the following:
• Node-positive disease, defined by the presence of metastatic breast cancer in 1 or more axillary or intramammary nodes
• At least 6 axillary or intramammary nodes must have been histologically examined
• Malignant involvement must be detectable by routine pathologic examination with hematoxylin and eosin staining
• Patients with immunohistologic staining as the only evidence of nodal involvement are considered node-negative
• Node-negative disease AND tumor at least 2 cm
• At least 6 nodes must be negative
• Node-negative status may be based on removal of fewer than 6 axillary nodes provided sentinel node procedure was performed
• Bilateral synchronous breast cancer diagnosed within 1 month of each other allowed provided the higher TNM stage primary tumor meets the eligibility criteria
• Prior modified radical mastectomy OR local excision of all tumors with axillary lymph node dissection or sentinel node resection required
• No more than 84 days since prior surgery for the primary tumor and/or axilla
• Final resection margins for the primary tumor must be histologically negative for invasive cancer and ductal carcinoma in situ
• Resection margins positive for lobular carcinoma in situ are allowed
• Hormone receptor status:
• Estrogen receptor status known
• Progesterone receptor status known

PATIENT CHARACTERISTICS: Age

• 18 and over

Sex

• Male or female

Menopausal status

• Not specified

Performance status

• Zubrod 0-2

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count at least 1,200/mm^3
• Platelet count at least 100,000/mm^3

Hepatic

• Bilirubin no greater than upper limit of normal (ULN)
• Alkaline phosphatase no greater than 2 times ULN
• SGOT or SGPT no greater than 2 times ULN

Renal

• Creatinine no greater than ULN

Cardiovascular

• No congestive heart failure
• No angina pectoris
• LVEF greater than the lower limit of normal* by MUGA or echocardiogram NOTE: Patients age 60 and over OR with a history of hypertension

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or adequately treated stage I or II cancer currently in complete remission
• HIV negative

PRIOR CONCURRENT THERAPY: Biologic therapy

• Not specified

Chemotherapy

• No prior cytotoxic chemotherapy for this breast cancer
• No prior chemotherapy with an anthracycline, anthracenedione, or taxane

Endocrine therapy

• Not specified

Radiotherapy

• No prior radiotherapy for this malignancy
• At least 2 weeks since prior radiotherapy for ductal carcinoma in situ

Surgery

• See Disease Characteristics

Alabama
      MBCCOP - Gulf Coast, Mobile,  Alabama,  36607,  United States; Recruiting
Arizona
      Arizona Cancer Center at University of Arizona Health Sciences Center, Tucson,  Arizona,  85724,  United States; Recruiting
      CCOP - Western Regional, Arizona, Phoenix,  Arizona,  85006-2726,  United States; Recruiting
      Veterans Affairs Medical Center - Phoenix (Carl T. Hayden), Phoenix,  Arizona,  85012,  United States; Recruiting
      Veterans Affairs Medical Center - Tucson, Tucson,  Arizona,  85723,  United States; Recruiting
Arkansas
      Arkansas Cancer Research Center at University of Arkansas for Medical Sciences, Little Rock,  Arkansas,  72205,  United States; Recruiting
      Veterans Affairs Medical Center - Little Rock, Little Rock,  Arkansas,  72205,  United States; Recruiting
California
      CCOP - Bay Area Tumor Institute, Oakland,  California,  94609-3305,  United States; Recruiting
      CCOP - Santa Rosa Memorial Hospital, Santa Rosa,  California,  95403,  United States; Recruiting
      Chao Family Comprehensive Cancer Center at University of California Irvine Cancer Center, Orange,  California,  92868,  United States; Recruiting
      City of Hope Comprehensive Cancer Center, Duarte,  California,  91010-3000,  United States; Recruiting
      Jonsson Comprehensive Cancer Center, UCLA, Los Angeles,  California,  90095-1781,  United States; Recruiting
      USC/Norris Comprehensive Cancer Center and Hospital, Los Angeles,  California,  90033,  United States; Recruiting
      Veterans Affairs Medical Center - Loma Linda (Pettis), Loma Linda,  California,  92357,  United States; Recruiting
      Veterans Affairs Outpatient Clinic - Martinez, Martinez,  California,  94553,  United States; Recruiting
Colorado
      University of Colorado Cancer Center at University of Colorado Health Sciences Center, Aurora,  Colorado,  80010,  United States; Recruiting
      Veterans Affairs Medical Center - Denver, Denver,  Colorado,  80220,  United States; Recruiting
District of Columbia
      MBCCOP - Howard University Cancer Center, Washington,  District of Columbia,  20060,  United States; Recruiting
Florida
      Veterans Affairs Medical Center - Tampa (Haley), Tampa,  Florida,  33612,  United States; Recruiting
Georgia
      CCOP - Atlanta Regional, Atlanta,  Georgia,  30342-1701,  United States; Recruiting
Hawaii
      MBCCOP - Hawaii, Honolulu,  Hawaii,  96813,  United States; Recruiting
Illinois
      Cardinal Bernardin Cancer Center at Loyola University Medical Center, Maywood,  Illinois,  60153-5500,  United States; Recruiting
      CCOP - Central Illinois, Decatur,  Illinois,  62526,  United States; Recruiting
      MBCCOP - University of Illinois at Chicago, Chicago,  Illinois,  60612,  United States; Recruiting
      Veterans Affairs Medical Center - Chicago (Westside Hospital), Chicago,  Illinois,  60612,  United States; Recruiting
      Veterans Affairs Medical Center - Hines (Edward Hines, Junior Hospital), Hines,  Illinois,  60141,  United States; Recruiting
Kansas
      CCOP - Wichita, Wichita,  Kansas,  67214-3882,  United States; Recruiting
      Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center, Kansas City,  Kansas,  66160-7353,  United States; Recruiting
      Veterans Affairs Medical Center - Wichita, Wichita,  Kansas,  67218,  United States; Recruiting
Kentucky
      Markey Cancer Center at University of Kentucky Chandler Medical Center, Lexington,  Kentucky,  40536-0084,  United States; Recruiting
      Veterans Affairs Medical Center - Lexington, Lexington,  Kentucky,  40502-2236,  United States; Recruiting
Louisiana
      Louisiana State University Health Sciences Center - Shreveport, Shreveport,  Louisiana,  71130-3932,  United States; Recruiting
      MBCCOP - LSU Health Sciences Center, New Orleans,  Louisiana,  70112,  United States; Recruiting
      Tulane Cancer Center at Tulane University Hospital and Clinic, New Orleans,  Louisiana,  70112,  United States; Recruiting
      Veterans Affairs Medical Center - New Orleans, New Orleans,  Louisiana,  70112,  United States; Recruiting
      Veterans Affairs Medical Center - Shreveport, Shreveport,  Louisiana,  71101-4295,  United States; Recruiting
Massachusetts
      Cancer Research Center at Boston Medical Center, Boston,  Massachusetts,  02118,  United States; Recruiting
Michigan
      Barbara Ann Karmanos Cancer Institute, Detroit,  Michigan,  48201-1379,  United States; Recruiting
      CCOP - Beaumont, Royal Oak,  Michigan,  48073-6769,  United States; Recruiting
      CCOP - Grand Rapids, Grand Rapids,  Michigan,  49503,  United States; Recruiting
      CCOP - Michigan Cancer Research Consortium, Ann Arbor,  Michigan,  48106,  United States; Recruiting
      Josephine Ford Cancer Center at Henry Ford Hospital, Detroit,  Michigan,  48202,  United States; Recruiting
      Providence Cancer Institute at Providence Hospital, Southfield,  Michigan,  48075,  United States; Recruiting
      University of Michigan Comprehensive Cancer Center, Ann Arbor,  Michigan,  48109-0912,  United States; Recruiting
      Veterans Affairs Medical Center - Ann Arbor, Ann Arbor,  Michigan,  48105,  United States; Recruiting
      Veterans Affairs Medical Center - Detroit, Detroit,  Michigan,  48201-1932,  United States; Recruiting
Mississippi
      University of Mississippi Medical Center, Jackson,  Mississippi,  39216-4505,  United States; Recruiting
      Veterans Affairs Medical Center - Jackson, Jackson,  Mississippi,  39216,  United States; Recruiting
Missouri
      CCOP - Cancer Research for the Ozarks, Springfield,  Missouri,  65807,  United States; Recruiting
      CCOP - Kansas City, Kansas City,  Missouri,  64131,  United States; Recruiting
      CCOP - St. Louis-Cape Girardeau, Saint Louis,  Missouri,  63141,  United States; Recruiting
      St. Louis University Hospital Cancer Center, Saint Louis,  Missouri,  63110,  United States; Recruiting
Montana
      CCOP - Montana Cancer Consortium, Billings,  Montana,  59101,  United States; Recruiting
New Mexico
      MBCCOP - University of New Mexico HSC, Albuquerque,  New Mexico,  87131,  United States; Recruiting
      Veterans Affairs Medical Center - Albuquerque, Albuquerque,  New Mexico,  87108-5138,  United States; Recruiting
New York
      Herbert Irving Comprehensive Cancer Center at Columbia University, New York,  New York,  10032,  United States; Recruiting
      James P. Wilmot Cancer Center at University of Rochester Medical Center, Rochester,  New York,  14642,  United States; Recruiting
      NYU School of Medicine's Kaplan Comprehensive Cancer Center, New York,  New York,  10016,  United States; Recruiting
North Carolina
      CCOP - Southeast Cancer Control Consortium, Goldsboro,  North Carolina,  27534-9479,  United States; Recruiting
Ohio
      CCOP - Columbus, Columbus,  Ohio,  43206,  United States; Recruiting
      CCOP - Dayton, Dayton,  Ohio,  45429,  United States; Recruiting
      Charles M. Barrett Cancer Center at University Hospital, Cincinnati,  Ohio,  45267-0501,  United States; Recruiting
      Cleveland Clinic Taussig Cancer Center, Cleveland,  Ohio,  44195-9001,  United States; Recruiting
      Veterans Affairs Medical Center - Cincinnati, Cincinnati,  Ohio,  45220-2288,  United States; Recruiting
      Veterans Affairs Medical Center - Dayton, Dayton,  Ohio,  45428-1002,  United States; Recruiting
Oklahoma
      Oklahoma University Medical Center, Oklahoma City,  Oklahoma,  73104,  United States; Recruiting
Oregon
      Cancer Institute at Oregon Health and Science University, Portland,  Oregon,  97201-3098,  United States; Recruiting
      CCOP - Columbia River Oncology Program, Portland,  Oregon,  97225,  United States; Recruiting
      Veterans Affairs Medical Center - Portland, Portland,  Oregon,  97207,  United States; Recruiting
South Carolina
      CCOP - Greenville, Greenville,  South Carolina,  29615,  United States; Recruiting
      CCOP - Upstate Carolina, Spartanburg,  South Carolina,  29303,  United States; Recruiting
      Hollings Cancer Center at Medical University of South Carolina, Charleston,  South Carolina,  29425,  United States; Recruiting
      Veterans Affairs Medical Center - Charleston, Charleston,  South Carolina,  29401-5799,  United States; Recruiting
Tennessee
      University of Tennessee Cancer Institute, Memphis,  Tennessee,  38104,  United States; Recruiting
      Veterans Affairs Medical Center - Memphis, Memphis,  Tennessee,  38104,  United States; Recruiting
Texas
      Brooke Army Medical Center, Fort Sam Houston,  Texas,  78234-6200,  United States; Recruiting
      CCOP - Scott and White Hospital, Temple,  Texas,  76508,  United States; Recruiting
      Harrington Cancer Center, Amarillo,  Texas,  79106,  United States; Recruiting
      University of Texas - MD Anderson Cancer Center, Houston,  Texas,  77030-4095,  United States; Recruiting
      University of Texas Health Science Center at San Antonio, San Antonio,  Texas,  78229-3900,  United States; Recruiting
      University of Texas Medical Branch, Galveston,  Texas,  77555-0565,  United States; Recruiting
      Veterans Affairs Medical Center - Amarillo, Amarillo,  Texas,  79106,  United States; Recruiting
      Veterans Affairs Medical Center - San Antonio (Murphy), San Antonio,  Texas,  78229,  United States; Recruiting
      Veterans Affairs Medical Center - Temple, Temple,  Texas,  76504,  United States; Recruiting
Utah
      Huntsman Cancer Institute, Salt Lake City,  Utah,  84112-5550,  United States; Recruiting
      Veterans Affairs Medical Center - Salt Lake City, Salt Lake City,  Utah,  84148,  United States; Recruiting
Washington
      CCOP - Northwest, Tacoma,  Washington,  98405-0986,  United States; Recruiting
      CCOP - Virginia Mason Research Center, Seattle,  Washington,  98101,  United States; Recruiting
      Puget Sound Oncology Consortium, Seattle,  Washington,  98109,  United States; Recruiting
      Veterans Affairs Medical Center - Seattle, Seattle,  Washington,  98108,  United States; Recruiting

Study chairs or principal investigators

George Thomas Budd, MD,  Cleveland Clinic Cancer Center   
Halle C.F. Moore, MD,  Cleveland Clinic Cancer Center   

Study ID Numbers:  CDR0000334899; SWOG-S0221
Record last reviewed:  September 2004
Record first received:  October 3, 2003
ClinicalTrials.gov Identifier:  NCT00070564
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2004-11-08