Filgrastim Plus Chemotherapy Compared With Filgrastim Alone In Treating Women Undergoing Peripheral Stem Cell Transplantation For Breast Cancer

OBJECTIVES:

I. Determine whether high dose chemotherapy in addition to growth factors increases the yield
of filgrastim mobilized progenitor cells.

II. Determine the kinetics of hematopoietic reconstitution following myeloablative therapy
and mobilized blood stem cell transplantation.

III. Determine whether the use of high dose chemotherapy in addition to growth factors for
mobilization of stem cells reduces risk of relapse as measured by time to progression in
responsive relapsed breast cancer patients receiving autologous peripheral blood stem cell or
bone marrow transplants.

IV. Determine the morbidity and cost differences of the use of high dose chemotherapy plus
growth factors compared to growth factors alone for mobilization of peripheral blood
progenitors and treatment of breast cancer with high dose chemotherapy.

OUTLINE: Patients will be randomized into 2 groups. Group 1 patients undergo CVP chemotherapy
treatment by vein (IV) on days 1-3, with cyclophosphamide (CTX), etoposide, and cisplatin.
Filgrastim SC (subcutaneously) is given on day 4 every 12 hours until completion of
apheresis. Group 2 patients only receive filgrastim SC given on day 1 every 12 hours until
completion of apheresis. Stem cells are removed beginning on day 4 for a maximum of 6 days.
Upon recovery of hematopoiesis patients then receive high IV doses of CBT chemotherapy with
CTX, carmustine, and thiotepa for 3 days, followed 4 days later by autologous stem cell
reinfusion. Beginning on day of reinfusion, filgrastim is given bid until WBC reaches a safe
level. Patients are followed for 90 days posttransplant, and then followed indefinitely for
antitumor response and time to progression.

PROJECTED ACCRUAL: This study will include about 218 patients.

DISEASE CHARACTERISTICS: Female patients with Stage II, III or IV breast carcinoma in
remission, and not eligible for protocols of higher priority (DM89-102) Stage II breast
cancer must have spread to at least 10 axillary nodes; patients with fewer than 10 nodes
must have extranodal extensions Patients with greater than 75% positive nodes for tumor are
eligible No bone marrow involvement with tumor by standard histopathological exam of
bilateral iliac marrow biopsies 2 weeks prior to study Prior normalization of markers
needed in patients with elevated tumor markers (e.g., CEA) Metastatic disease patients must
have documentation verifying at least 50% reduction of all sites of disease, except bone
Stable bone metastases measured via bone scan are eligible Responsive disease but with
large tumor burden should enter high risk BMT protocols (93-090)

PATIENT CHARACTERISTICS: Age: 18 to 65 Performance status: Zubrod 0-1 Life expectancy: Not
specified Hematopoietic: WBC greater than 3,000/mm3 Platelet count greater than 100,000/mm3
No hematopoietic growth factor treatments Hepatic: Bilirubin, SGOT, and SGPT less than 2
times normal Renal: Estimated creatinine clearance greater than 60 mL/min Cardiovascular:
Normal ejection fraction Pulmonary: DLCO greater than 50% of predicted Other: Not HIV
positive Not pregnant 2 weeks prior to study No comorbid condition placing patient at high
risk for complications No prior active infections No history of untreated central nervous
system (CNS) disease No allergic response to eggs or murine protein

PRIOR CONCURRENT THERAPY: No concurrent involvement in any other clinical trial that
effects engraftment Biologic therapy: No growth factors within 1 week Chemotherapy: No more
than 2 chemotherapy regimens allowed after relapse for metastatic disease Chemotherapy
responsive disease prior to study Stage II/III disease receiving neoadjuvant chemotherapy
allowed with at least 4 positive nodes at mastectomy No partial response to chemotherapy
less than 50% of any site except bone No prior chemotherapy treatment with carmustine
Endocrine therapy: Not specified Radiotherapy: Not specified Surgery: Mastectomy allowed