Trial Information

A Phase III Study of High-Dose Chemotherapy Using Busulfan, Melphalan and Thiotepa Versus Cyclophosphamide,Thiotepa, Carboplatin Followed by Autologous Stem Cell Transplantation in Patients With High-Risk Primary Stage II or III (Non-Inflammatory) Breast Cancer

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.