Chemotherapy Plus Surgery in Treating Women With 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 surgery with chemotherapy may kill more tumor cells. It
      is not yet known which treatment regimen is more effective for breast cancer.

      PURPOSE: Randomized phase III trial to study the effectiveness of chemotherapy plus surgery
      in treating women who have breast cancer.
    

Detailed description: 
      OBJECTIVES:

        -  Evaluate whether 8 courses of primary chemotherapy before adequate surgery of breast
           tumor and locoregional radiotherapy plus tamoxifen for 5 years improves the disease-free
           and overall survival in women with operable breast carcinoma and tumor at diagnosis
           greater than 2 cm in diameter.

        -  Assess whether, in the postoperative arms, the addition of paclitaxel to doxorubicin
           before CMF (cyclophosphamide, methotrexate, and fluorouracil) improves disease-free and
           overall survival in these patients.

        -  Define the incidence of pathologic complete response (CR) induced by 8 courses of
           primary chemotherapy containing paclitaxel.

        -  Assess whether a pathologic CR is an independent predictor of disease-free and overall
           survival.

        -  Evaluate the effects of primary chemotherapy on the rate and quality of breast
           conserving surgery.

      OUTLINE: This is a randomized, multicenter study. Patients are stratified by center, tumor
      diameter at mammography, nuclear or histological grade, and estrogen/progesterone receptor
      status. Patients are randomized to one of three treatment arms.

        -  Arm I: Patients receive doxorubicin IV over 15 minutes once every 3 weeks for 4 courses.
           Beginning 21 days after the last administration of doxorubicin, patients receive
           cyclophosphamide IV, methotrexate IV, and fluorouracil IV on days 1 and 8. Treatment
           repeats every 28 days for 4 courses in the absence of disease progression or
           unacceptable toxicity.

        -  Arms II and III: Patients receive doxorubicin IV over 15 minutes and paclitaxel IV over
           3 hours once every 3 weeks for 4 courses. Beginning 21 days after the last
           administration of doxorubicin and paclitaxel, patients receive cyclophosphamide IV,
           methotrexate IV, and fluorouracil IV on days 1 and 8. Treatment repeats every 28 days in
           the absence of disease progression or unacceptable toxicity.

      All patients have either mastectomy or breast conserving surgery; patients with unclear
      surgical margins may have second surgery (re-resection or total mastectomy) or radiotherapy.
      Lymph node axillary dissection is performed up to at least the second level. For patients in
      the 2 adjuvant arms (arms I and II), adjuvant chemotherapy starts by day 21 after surgery.
      For patients in the primary chemotherapy arm (arm III), surgery is performed by day 28 after
      the last course of chemotherapy or at resolution of all possible hematological or infective
      complications.

      At the end of the combined surgery plus chemotherapy approach (i.e., after the last course of
      CMF (arms I and II) or after surgery (arm III)), patients enrolled after June 30, 2000 with
      estrogen or progesterone receptor positive disease receive oral tamoxifen daily for 5 years.

      All patients who have breast conserving surgery receive postoperative irradiation within 4
      weeks after completing chemotherapy and surgery (i.e., within 4 weeks from last dose of
      adjuvant chemotherapy (arms I and II) or from surgery (arm III)). All patients who have
      mastectomy and have pT4 disease must receive irradiation to the chest wall.

      Patients are followed at 6, 12, 18, and 24 months, and then annually thereafter.

      PROJECTED ACCRUAL: A total of 450 patients per arm will be accrued for this study within 5
      years.
    

Intervention name(s): CMF regimen; cyclophosphamide; doxorubicin hydrochloride; fluorouracil; methotrexate; paclitaxel; tamoxifen citrate; conventional surgery; radiation therapy
Intervention type(s): Drug; Drug; Drug; Drug; Drug; Drug; Drug; Procedure; Radiation
Intervention MeSH terms: Tamoxifen; Paclitaxel; Cyclophosphamide; Doxorubicin; Liposomal doxorubicin; Fluorouracil; Methotrexate
Allocation: Randomized
Primary purpose: Treatment
Keywords: stage II breast cancer; stage IIIA breast cancer