Combination Chemotherapy in Treating Women With Stage I, Stage II, or Stage IIIA (cT1-3, N0-1, M0) Breast Cancer and Positive Axillary Lymph Nodes
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: cyclophosphamide; docetaxel; doxorubicin
Intervention description: Arm 1: 600 mg/m2 IV every 21 days for 4 cycles; Arm 3: 500 mg/m2 IV every 21 days for 4 cycles; Arm 1: 100 mg/m2 IV every 21 days for 4 cycles; Arms 2 and 3: 75 mg/m2 IV every 21 days for 4 cycles; Arm 1: 60 mg/m2 IV every 21 days for 4 cycles; Arms 2 and 3: 50 mg/m2 IV every 21 days for 4 cycles
Intervention MeSH terms: Cyclophosphamide; Docetaxel; Doxorubicin
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 5351.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: stage I breast cancer; stage II breast cancer; stage IIIA breast cancer

Summary:

      RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so
      they stop growing or die. Giving combination chemotherapy after surgery may kill any tumor
      cells remaining following surgery. It is not yet known which regimen of combination
      chemotherapy is more effective in treating breast cancer with positive axillary lymph nodes.

      PURPOSE: Randomized phase III trial to compare the effectiveness of different regimens of
      combination chemotherapy in treating women who have undergone surgery for stage I, stage II,
      or stage IIIA breast cancer with positive axillary lymph nodes.
    

Eligibility criteria:

        DISEASE CHARACTERISTICS:

          -  Histologically confirmed invasive adenocarcinoma of the breast

               -  Confined to the breast and ipsilateral axilla on clinical exam

                    -  Stage I, II, or IIIA (cT1-3, N0-1, M0)

          -  At least one axillary lymph node with evidence of tumor on histologic exam

               -  Sentinel node biopsy allowed if followed by axillary dissection

               -  No suspicious palpable nodes in the contralateral axilla or palpable
                  supraclavicular or infraclavicular nodes, unless proven on biopsy to not be
                  involved with tumor

          -  No bilateral malignancy or mass in the opposite breast, unless mass is histologically
             proven to be benign

          -  Must have undergone either a prior total mastectomy and axillary dissection (modified
             radical mastectomy) OR

          -  Prior lumpectomy and axillary dissection

               -  Patients must receive radiotherapy after randomization (not before) AND after
                  chemotherapy

               -  Margins must be clear

               -  No ipsilateral lymph nodes that are fixed to one another or to other structures
                  (N2 disease) and/or any positive nonaxillary lymph nodes (intramammary nodes are
                  considered axillary nodes)

               -  No histologically evident invasive tumor or ductal carcinoma in situ

               -  No diffuse tumors by mammography that would not be surgically amenable to
                  lumpectomy

               -  No other dominant mass in the ipsilateral breast remnant unless one of the
                  following is true:

                    -  Histologically benign

                    -  Surgically removed with clear margins if malignant

          -  No ulceration, erythema, infiltration of the skin or underlying chest wall (complete
             fixation), peau d'orange, or skin edema of any magnitude

               -  Tethering or dimpling of the skin or nipple inversion allowed

          -  No metastatic disease

               -  Skeletal pain allowed if bone scan negative for metastases

          -  Hormone receptor status:

               -  Estrogen and progesterone status determined

        PATIENT CHARACTERISTICS:

        Age:

          -  greater than or equal to 18 years

        Sex:

          -  Female

        Menopausal status:

          -  Not specified

        Performance status:

          -  Not specified

        Life expectancy:

          -  At least 10 years, excluding diagnosis of cancer

        Hematopoietic:

          -  Absolute neutrophil count at least 1,500/mm^3 (may be less, if in the opinion of the
             investigator, this represents an ethnic or racial variation)

          -  Platelet count at least 100,000/mm^3* NOTE: *If platelet count is above the upper
             limit of normal (ULN), significant underlying hematologic disorders must be excluded

        Hepatic:

          -  Bilirubin no greater than ULN

          -  Alkaline phosphatase less than 2.5 times ULN*

          -  SGOT less than 1.5 times ULN*

          -  No nonmalignant systemic hepatic disease that would preclude study participation NOTE:
             *Alkaline phosphatase and SGOT cannot both be greater than ULN

        Renal:

          -  Creatinine no greater than normal

          -  No nonmalignant systemic renal disease that would preclude study participation

        Cardiovascular:

          -  No nonmalignant systemic cardiovascular disease that would preclude study
             participation

          -  LVEF at least lower limit of normal (LLN) by MUGA or echocardiogram

          -  No active cardiac disease that would preclude use of doxorubicin or docetaxel,
             including the following:

               -  Any prior myocardial infarction

               -  Angina pectoris requiring anti-anginal medication

               -  History of congestive heart failure

               -  Cardiac arrhythmia requiring medication

               -  Severe conduction abnormality

               -  Valvular disease with documented cardiac function compromise

               -  Cardiomegaly on chest x-ray or ventricular hypertrophy on EKG, unless LVEF at
                  least LLN

               -  Poorly controlled hypertension (diastolic greater than 100 mm/Hg)

               -  Hypertension well controlled by medication allowed

        Other:

          -  No grade 2 or greater peripheral neuropathy

          -  No other prior malignancy within the past 5 years except:

               -  Effectively treated squamous cell or basal cell skin cancer

               -  Surgically treated carcinoma in situ of the cervix

               -  Segmentally resected lobular carcinoma in situ of the ipsilateral or
                  contralateral breast

          -  Not pregnant or nursing

          -  Negative pregnancy test

          -  Fertile patients must use effective barrier contraception

          -  No nonmalignant systemic disease that would preclude study participation

          -  No diabetes with morning fasting blood glucose of 200 mg/dL or greater

          -  No psychiatric or addictive disorders that would preclude informed consent

          -  No contraindication to corticosteroids that would preclude study participation

        PRIOR CONCURRENT THERAPY:

        Biologic therapy:

          -  No prior immunotherapy for breast cancer

        Chemotherapy:

          -  No prior chemotherapy for breast cancer

          -  No prior anthracyclines or taxanes

          -  No other concurrent investigational chemotherapy

        Endocrine therapy:

          -  No prior hormonal therapy for breast cancer

          -  No concurrent hormonal birth control methods or other hormonal therapy

          -  No concurrent raloxifene, including for osteoporosis

          -  Concurrent low-dose topical estrogen in the form of conjugated estrogen ring or
             conjugated estrogen vaginal cream (dose no more than 0.3 mg or 1/8 of an applicator
             applied vaginally 3 times a week) allowed

        Radiotherapy:

          -  See Disease Characteristics

          -  No prior radiotherapy for this malignancy

        Surgery:

          -  See Disease Characteristics

          -  No more than 84 days since prior surgery for breast cancer (e.g., lumpectomy,
             mastectomy, sentinel node biopsy, axillary dissection, or re-excision of lumpectomy
             margins)

        Other:

          -  No prior systemic therapy for this malignancy

          -  No concurrent medications that alter cardiac conduction (e.g., digitalis, beta
             blockers, or calcium-channel blockers) for cardiac arrhythmia, angina, or congestive
             heart failure (allowed if administered for other reasons [e.g., hypertension])

          -  Concurrent bisphosphonates allowed