Combination Chemotherapy and Peripheral Stem Cell Transplantation in Treating Patients With Stage II or Stage IIIA Breast Cancer
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Study type: Interventional
Phase: Phase 3

Summary: 
      RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so
      they stop growing or die. Combining chemotherapy with peripheral stem cell transplantation
      may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells. It
      is not yet known which regimen of combination chemotherapy is more effective for breast
      cancer.

      PURPOSE: Randomized phase III trial to compare the effectiveness of two regimens of
      combination chemotherapy followed by peripheral stem cell transplantation in treating
      patients who have stage II or stage IIIA breast cancer.
    

Detailed description: 
      OBJECTIVES: I. Compare early mortality, survival, and disease free survival in patients with
      node positive stage II or IIIA breast cancer treated with busulfan, melphalan, and thiotepa
      versus cyclophosphamide, thiotepa, and carboplatin followed by autologous peripheral blood
      stem cell transplantation. II. Compare the toxicity of these 2 regimens in this patient
      population.

      OUTLINE: This is a randomized study. Patients are stratified according to stage of disease
      (stage II vs stage IIIA), lymph node status (at least 10 positive nodes vs less than 10
      positive nodes), and hormone receptor status (estrogen receptor positive or progesterone
      receptor positive vs estrogen receptor negative or progesterone receptor negative). All
      patients initially receive mobilization chemotherapy with cyclophosphamide IV over 1-2 hours
      on day 1 and paclitaxel IV over 4 hours on day 2. Beginning on day 4, patients receive
      filgrastim (G-CSF) or sargramostim (GM-CSF) subcutaneously each day until the final day of
      leukapheresis. When blood counts recover, peripheral blood stem cells (PBSC) are harvested.
      Patients are randomized to 1 of 2 high dose chemotherapy regimens 28-45 days after the last
      dose of mobilization chemotherapy. Arm I: Patients receive oral busulfan every 6 hours on
      days -8 to -6, melphalan IV over 30-60 minutes on days -5 and -4, and thiotepa IV over 2
      hours on days -3 and -2. PBSC are reinfused on day 0. Arm II: Patients receive
      cyclophosphamide, thiotepa, and carboplatin by continuous IV infusion over 24 hours on days
      -7, to -4. PBSC are reinfused on day 0. Beginning 4-6 weeks after the last dose of
      chemotherapy, patients in both arms receive local radiotherapy 5 days each week for 5 weeks.
      Patients also receive oral tamoxifen (or equivalent antiestrogen therapy) daily for 5 years
      if they are estrogen or progesterone receptor positive, postmenopausal, or age 50 and over
      and perimenopausal. Patients are followed every 3 months for 2 years and then every 6 months
      thereafter.

      PROJECTED ACCRUAL: A total of 280 patients (140 per treatment arm) will be accrued for this
      study over 3 years.
    

Intervention name(s): filgrastim; sargramostim; busulfan; carboplatin; cyclophosphamide; melphalan; paclitaxel; tamoxifen citrate; thiotepa; peripheral blood stem cell transplantation; radiation therapy
Intervention type(s): Biological; Biological; Drug; Drug; Drug; Drug; Drug; Drug; Drug; Procedure; Radiation
Intervention MeSH terms: Tamoxifen; Paclitaxel; Cyclophosphamide; Carboplatin; Melphalan; Busulfan; Thiotepa; Sargramostim
Allocation: Randomized
Primary purpose: Treatment
Keywords: stage II breast cancer; stage IIIA breast cancer