Primary Chemotherapy With Docetaxel-Capecitabine and Doxorubicin-Cyclophosphamide in Breast Cancer
Condition: Breast Cancer; Breast Neoplasm
MeSH terms: Breast Neoplasms
Intervention: Docetaxel - Dose A; Anastrozole; cyclophosphamide; Docetaxel - Dose B; Doxorubicin hydrochloride; Tamoxifen Citrate; Capecitabine - Dose B; Capecitabine - Dose A
Intervention description: Dose A-Cohort 1 Docetaxel 75 mg/m^2 intravenous day 1; 1 mg orally daily for five years; 600 mg/m^2 will be diluted in 100 mL 0.9% normal saline (NS) and administered intravenously over 30 minutes on day 1; Dose B - Cohort 2 Docetaxel 60 mg/m^2 intravenous day 1; 60 mg/m^2 will be administered as a slow intravenous push on day 1; 20 mg/day orally for five years; Dose B - Cohort 2 capecitabine 937.5 mg/m^2 orally twice daily day 2-15; capecitabine 1000 mg/m^2 orally twice daily day 2-15 for 4 cycles
Intervention MeSH terms: Tamoxifen; Cyclophosphamide; Docetaxel; Doxorubicin; Liposomal doxorubicin; Capecitabine; Anastrozole
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 30.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: cDNA Microarray; Stage II and Stage III Breast Cancer; Biological Response; Molecular Profiling; Fine Needle Aspirate; Breast Cancer

Summary:

      This study will assess the usefulness of a technique called complementary deoxyribonucleic
      acid (cDNA) microarray-an examination of a wide array of genes to identify disease-associated
      patterns-for measuring tumor response to chemotherapy in breast cancer patients. The study
      will look for "markers" that can help select the most effective type of chemotherapy. It will
      also evaluate the safety and effectiveness of a new drug combination of capecitabine and
      docetaxel.

      Patients age 18 years and older with stage II or III breast cancer whose tumor is 2
      centimeters or larger may be eligible for this study. Those enrolled will be treated with
      surgery, standard chemotherapy using doxorubicin (Adriamycin) and cyclophosphamide (Cytoxan),
      and the capecitabine and docetaxel combination.

      Patients will have a physical examination, mammogram and magnetic resonance imaging to
      evaluate their tumor before beginning treatment. They will then have four 21-day treatment
      cycles of docetaxel and capecitabine, as follows: docetaxel intravenously (through a vein) on
      day 1 and capecitabine pills (by mouth) twice a day from days 2 through 15. No drugs will be
      given from days 16 through 21. This regimen will be repeated four times, after which the
      tumor will be re-evaluated by physical examination, mammogram, and magnetic resonance
      imaging.

      Patients will then have surgery to remove the cancer-either lumpectomy with removal of the
      underarm lymph nodes; mastectomy and removal of the underarm lymph nodes; or modified radical
      mastectomy. After recovery, they will have four more cycles of chemotherapy, this time with a
      doxorubicin and cyclophosphamide. Both drugs will be given intravenously on day 1 of four
      21-day cycles.

      Some patients who had a mastectomy (depending on their tumor characteristics and whether
      tumor cells were found in their lymph nodes) and all those who had a lumpectomy will also
      have radiation therapy. Patients with hormone receptor-positive tumors will also receive
      tamoxifen treatment for 5 years.

      In addition to the above procedures, all patients will have tumor biopsies (removal of a
      small piece of tumor tissue) before beginning treatment, on day 1 of cycle 1, before cycle 2,
      and at the time of surgery, and physical examinations, chest X-rays, bone scans, computerized
      tomography (CT) scans, electrocardiograms, multi-gated acquisition scan-MUGA (nuclear
      medicine test of cardiac function) or echocardiograms of heart function, mammograms and blood
      tests at various times during the study. Patients will be followed at National Institutes of
      Health (NIH) for 3 years after diagnosis with physical examinations, blood tests, X-rays, and
      computed tomography (CT) scans.

      Although it is not known whether this treatment will help an individual patient's cancer,
      possible benefits are tumor shrinkage and decreased risk of disease recurrence. In addition,
      the information gained about genetic changes after chemotherapy will help determine if
      additional studies on the use of cDNA microarray to measure tumor response are warranted.
    

Eligibility criteria:

        -  INCLUSION CRITERIA:

        Stage II or III breast cancer with a tumor size of greater than 2 cm. Patients with a
        previous biopsy are eligible provided adequate tumor tissue remains for biopsy in this
        study.

        At least 18 years of age.

        Adequate hematopoietic function as defined by absolute neutrophil count greater than
        1200/mm^3 and platelet count greater than 100,000/mm^3.

        Adequate renal function as defined by creatinine less than 1.6 mg/dL.

        Adequate hepatic function as defined by total (T.) bilirubin less than 1.4 mg/dL and serum
        glutamic oxaloacetic transaminase (SGOT)/serum glutamic pyruvic transaminase (SGPT) less
        than 1.5 times the upper limit of normal and alkaline phosphatase less than 2.5 times upper
        limit of normal

        Zubrod Performance status 0-2.

        EXCLUSION CRITERIA:

        Medical or psychiatric condition that, in the opinion of the Principal Investigator, would
        preclude chemotherapy administration. Patients may be evaluated by psychiatry or medical
        subspecialties as appropriate.

        Pregnant or lactating women

        Known bleeding disorders

        Hypersensitivity to Tween 80 (Polysorbate)

        Cardiac ejection fraction below normal limits, myocardial infarction within the past 12
        months, or symptomatic arrhythmia requiring medical intervention.

        Prior chemotherapy or hormonal therapy for breast cancer. Patients treated with hormonal
        chemoprevention (tamoxifen or raloxifene) will be eligible.

        Active malignancy diagnosed within the last 5 years. (Cervical cancer or non-melanomatous
        skin cancer that has been treated with curative intent will be eligible).