Trial Information

A Pilot Trial Comparing Doxorubicin and Paclitaxel Induced Apoptosis in Locally Advanced Breast Cancer

OBJECTIVES: I. Assess the feasibility of obtaining serial biopsies in patients receiving
neoadjuvant chemotherapy for locally advanced breast cancer. II. Assess the feasibility of
performing assays of apoptosis and of markers that predict response on specimens obtained in
these patients. III. Correlate the results of the assays with clinical and pathologic
response rates. IV. Establish a baseline of change in apoptosis rates for future studies. V.
Obtain serial blood samples and tumor tissue for future biological studies.

OUTLINE: This is a randomized study. Patients are stratified by pre or postmenopausal state
and T3 or T4 lesions. Arm I: Patients receive single agent doxorubicin by bolus infusion on
day 1. Dose repeats every 14 days for a total of four courses, provided absolute neutrophil
count (ANC) and platelet count remain in the appropriate range. Patients then receive
paclitaxel IV administered over 3 hours once every 14 days for a total of four courses,
provided ANC and platelet count remain in the appropriate range. Filgrastim (G-CSF)
subcutaneous treatment is started on day 3 of each course, and continued for 7 days, or
until ANC is greater than 10,000/mm3. Patients undergo serial core-needle breast biopsies or
fine needle aspirations prior to starting therapy and on day one of each course. Arm II:
Patients receive four courses of paclitaxel given once every 14 days. Patients then receive
four courses of doxorubicin given on day 1 every 14 days, provided ANC and platelet count
are in the appropriate range. G-CSF subcutaneous treatment is started on day 3 of each
course, as in Arm I. Patients undergo serial core-needle breast biopsies or fine needle
aspirations prior to starting and on day one of each course. Arm I and II: Upon completion
of eight courses of chemotherapy, patients undergo a surgical procedure to evaluate the
extent of residual disease and number of lymph nodes involved, and to achieve local control.
Following surgery, patients receive additional treatment at the discretion of the treating
oncologist. Eligible patients undergo further high dose chemotherapy with peripheral blood
stem cell rescue; other patients receive cyclophosphamide therapy. Patients receiving
lumpectomies receive breast irradiation. Patients receiving mastectomies might receive chest
wall irradiation. Following radiotherapy, hormone receptor positive patients may start
tamoxifen therapy for 5 years.

PROJECTED ACCRUAL: An estimated 40 patients (20 per treatment arm) will be accrued for this
study.