S0221 Adjuvant Doxorubicin, Cyclophosphamide, and Paclitaxel in Treating Patients With Breast Cancer
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: pegfilgrastim; AC regimen; cyclophosphamide; doxorubicin hydrochloride; paclitaxel
Intervention description: Given IV; Given IV; Given IV; Given IV; Given IV
Intervention MeSH terms: Paclitaxel; Cyclophosphamide; Doxorubicin; Liposomal doxorubicin
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 3294.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: stage II breast cancer; stage IA breast cancer; stage IB breast cancer; stage IIIC breast cancer; male breast cancer; HER2-positive breast cancer; estrogen receptor-negative breast cancer; estrogen receptor-positive breast cancer; progesterone receptor-negative breast cancer; progesterone receptor-positive breast cancer

Summary:

      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: This randomized phase III trial is comparing 2 different regimens of combination
      chemotherapy to see how well they work in treating patients who have undergone surgery for
      stage I, stage II, or stage III breast cancer.
    

Eligibility 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:

               -  Tumor ≥ 2 cm in greatest diameter (includes both invasive and intraductal
                  component)

                    -  Patients with nodal status of N0+ (i.e., no cluster of tumor cells in any
                       node greater than 0.2 mm) are considered to be node negative and must have a
                       primary tumor ≥ 2 cm in size or have a tumor ≥ 1 cm with high risk features

                    -  Patients who are node negative on the basis of a sentinel node procedure and
                       fewer than 6 axillary nodes are removed are eligible OR at least 6 axillary
                       or intramammary nodes must be negative

               -  Tumor ≥ 1 cm in diameter and meeting 1 of the following criteria:

                    -  ER-negative and PgR-negative

                    -  ER-positive or PgR-positive with a Genomic Health Recurrence Score of ≥ 26

               -  One or more axillary or intramammary nodes are involved by metastatic breast
                  cancer

                    -  If one or more nodes is involved, a minimum of 6 axillary or intramammary
                       nodes must have been examined histologically

                    -  Patients with N0(I+) disease will be considered node negative

          -  HER2/neu-positive tumors (3+ by immunohistochemical staining or amplified by
             fluorescence in-situ hybridization) allowed

          -  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 active angina pectoris

          -  LVEF greater than or equal to 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, in situ cervical carcinoma, or lobular carcinoma in situ of
             the breast

               -  Prior invasive breast cancer or ductal carcinoma in situ allowed if disease-free
                  for 5 years

          -  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