Trial Information

A Randomized Phase III Trial of Sequential Chemotherapy Using Doxorubicin, Paclitaxel, and Cyclophosphamide or Concurrent Doxorubicin and Cyclophosphamide Followed by Paclitaxel at 14 or 21 Day Intervals in Women With Node Positive Stage II/IIIA Breast Cancer

OBJECTIVES: I. Compare the sequential chemotherapy with doxorubicin, paclitaxel and
cyclophosphamide to combined doxorubicin and cyclophosphamide followed by paclitaxel for
disease free and overall survival in women with node positive stage II or IIIA breast
cancer. II. Determine whether increasing the dose density of adjuvant chemotherapy will
improve disease free and overall survival. III. Compare the toxicity in patients treated
with these regimens.

OUTLINE: This is a randomized study. Patients are randomized into one of four arms
(sequential chemotherapy every 2 weeks vs every 3 weeks vs concurrent chemotherapy followed
by paclitaxel every 2 weeks vs every 3 weeks). All tumor should be removed by either a
modified radical mastectomy or a segmental mastectomy plus axillary node dissection.
Adjuvant chemotherapy is started within 84 days following the last surgical procedure. Arm
I: Patients receive sequential chemotherapy every 3 weeks. Doxorubicin IV is administered
once every 3 weeks for 4 doses. Paclitaxel IV is then administered over 3 hours once every 3
weeks for 4 doses. Cyclophosphamide IV is administered once every 3 weeks for 4 doses
following paclitaxel. Arm II: Patients receive sequential chemotherapy every 2 weeks.
Doxorubicin IV is administered once every 2 weeks for 4 doses. Paclitaxel IV is then
administered over 3 hours once every 2 weeks for 4 doses. Cyclophosphamide IV is
administered once every 2 weeks for 4 doses following paclitaxel. Filgrastim (G-CSF) is
administered by subcutaneous injection on days 3-10 after each dose of doxorubicin,
paclitaxel, and cyclophosphamide. Arm III: Patients receive combination chemotherapy every 3
weeks. Combination doxorubicin IV and cyclophosphamide IV is administered once every 3 weeks
for 4 doses. Paclitaxel IV is administered over 3 hours once every 3 weeks for 4 doses
following combination chemotherapy. Arm IV: Patients receive combination chemotherapy every
2 weeks. Combination doxorubicin IV and cyclophosphamide IV is administered once every 2
weeks for 4 doses. Paclitaxel IV is administered over 3 hours once every 2 weeks for 4 doses
following combination chemotherapy. G-CSF is administered by subcutaneous injection on days
3-10 after each dose of doxorubicin/cyclophophamide and after each dose of paclitaxel. After
completion of all chemotherapy, patients receive tamoxifen orally for 5 years. Patients
undergo radiotherapy 4-6 weeks after the completion of chemotherapy. Patients are followed
every 6 months for 5 years, then annually until death.

PROJECTED ACCRUAL: A total of 2,000 patients will be accrued for this study within 22
months.