High-Dose Combination Chemotherapy Plus Peripheral Stem Cell Transplantation Compared With Standard Combination Chemotherapy in Treating Women With High-Risk 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 if high-dose combination chemotherapy plus peripheral stem cell
      transplantation is more effective than standard combination chemotherapy for breast cancer.

      PURPOSE: Randomized phase III trial to compare high-dose combination chemotherapy plus
      peripheral stem cell transplantation with standard combination chemotherapy in treating women
      with stage II or stage III breast cancer.
    

Detailed description: 
      OBJECTIVES: I. Compare the survival, disease-free survival, and systemic disease-free
      survival of women with high-risk, operable stage II/III breast cancer treated with three
      courses of dose-intensive epirubicin/cyclophosphamide (EC) supported by granulocyte
      colony-stimulating factor (G-CSF) and G-CSF-mobilized peripheral blood stem cells vs.
      standard EC followed by cyclophosphamide/methotrexate/fluorouracil. II. Compare the toxicity,
      duration of quality-adjusted time without symptoms and toxicity, and quality of life
      associated with these two treatments. III. Evaluate the cost effectiveness of these two
      treatments.

      OUTLINE: This is a randomized study. Patients are stratified by estrogen receptor status and
      menopausal status. Within 6 weeks of surgery, patients in the first group receive epirubicin
      (preferred) or doxorubicin plus cyclophosphamide every 3 weeks for 4 courses followed by
      conventional cyclophosphamide, methotrexate, and fluorouracil (CMF) every 4 weeks for 3
      courses. Patients in the second group undergo stem cell mobilization and harvest with
      granulocyte colony-stimulating factor (G-CSF) followed within 10 weeks of surgery by
      high-dose chemotherapy with epirubicin and cyclophosphamide followed by peripheral blood stem
      cell rescue and G-CSF. All patients receive adjuvant tamoxifen, and patients who underwent
      lumpectomy prior to entry are required to receive adjuvant radiotherapy (radiotherapy is
      optional for patients who underwent mastectomy prior to entry). Patients are followed every 3
      months for 2 years, then q 6 months for 3 years, then yearly.

      PROJECTED ACCRUAL: 210 patients will be accrued over 4 years to provide 195 evaluable
      patients.
    

Intervention name(s): filgrastim; CMF regimen; cyclophosphamide; doxorubicin hydrochloride; epirubicin hydrochloride; fluorouracil; mesna; methotrexate; tamoxifen citrate; peripheral blood stem cell transplantation; low-LET electron therapy; low-LET photon therapy
Intervention type(s): Biological; Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug; Procedure; Radiation; Radiation
Intervention description(s): Filgrastim 10 mg/kg/d sc for 6 days after randomization.; Cyclophosphamide 100 mg/m2 orally days 1 - 14, methotrexate 40 mg/m2 iv days 1 and 8, 5-fluorouracil 600 mg/m2 iv days 1 and 8. Repeat every 28 days.; For high-dose EC arm: cyclophosphamide 4 gm/m2 iv as 4 divided doses. For standard chemotherapy arm: cyclophosphamide 600 mg/m2 iv day 1 of 21-day EC cycles, and cyclophosphamide 100 mg/m2 orally on days 1-14 of 28-day CMF cycles.; Doxorubicin 60 mg/m2 iv on day 1 of 21-day cycles of AC.; Epirubicin 90 mg/m2 iv on day 1 of 21-day cycles of EC.; 5-fluorouracil 600 mg/m2 iv days 1 and 8 of 28-day cycles of CMF.; MESNA (7.2 gm/m2) on days 2 and 3 of 21-day cycles of dose-intensive EC.; Methotrexate 40 mg/m2 iv on days 1 and 8 of 28-day cycles of CMF.; Tamoxifen 20mg daily for 5 years or until relapse.; Peripheral blood progenitor cells (PBPC) infusion on day 5 of each 21-day cycle of dose-intensive EC.; Radiation therapy to the conserved breast is mandatory, to be carried out according to the prospectively defined guidelines of each participating institution; either after all chemotherapy or integrated into CMF as agreed per institution. Radiotherapy to the chest wall following mastectomy is optional according to the prospectively defined guidelines of each participating institution.; radiation therapy to the conserved breast is mandatory, to be carried out according to the prospectively defined guidelines of each participating institution; either after all chemotherapy or integrated into CMF as agreed per institution. Radiotherapy to the chest wall following mastectomy is optional according to the prospectively defined guidelines of each participating institution.
Intervention MeSH terms: Tamoxifen; Cyclophosphamide; Doxorubicin; Liposomal doxorubicin; Fluorouracil; Methotrexate; Epirubicin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: stage II breast cancer; stage IIIA breast cancer