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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

Phase 3
18 Years
65 Years
Not Enrolling
Breast Cancer

Thank you

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

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

PROJECTED ACCRUAL: A total of 280 patients (140 per treatment arm) will be accrued for this
study over 3 years.

Inclusion Criteria

DISEASE CHARACTERISTICS: Histologically proven stage II breast cancer with 1 of the
following: Estrogen receptor negative with at least 4 positive nodes OR Estrogen receptor
positive with at least 6 positive nodes OR Histologically proven stage IIIA breast cancer
Must have already received 4-7 courses of conventional chemotherapy with a doxorubicin
based regimen (which may include paclitaxel or docetaxel) No greater than 60 days since
induction chemotherapy Prior definitive surgical treatment of primary lesion (modified
radical mastectomy or breast conserving procedure plus axillary node dissection) Margins
free of tumor Hormone receptor status: Estrogen and progesterone receptor status known

PATIENT CHARACTERISTICS: Age: 18 to 65 Menopausal status: Not specified Performance
status: Karnofsky 70-100% Life expectancy: Not specified Hematopoietic: Not specified
Hepatic: Bilirubin no greater than 2.0 mg/dL SGOT or SGPT no greater than 2 times normal
Renal: Creatinine no greater than 2.0 mg/dL OR Creatinine clearance at least 60 mL/min
Cardiovascular: Left ventricular ejection fraction at least 50% if any of the following:
Symptoms of congestive heart failure Abnormal cardiac exam Prior doxorubicin dose greater
than 400 mg/m2 Pulmonary: No significant pulmonary disease (DLCO less than 60% predicted)
Other: Not pregnant Negative pregnancy test HIV negative No significant active infection
No other severe disease that would severely limit life expectancy No other malignancy
within past 5 years unless: Chance of survival for greater than 5 years is 90% AND Treated
with surgery only (no chemotherapy or radiotherapy)

PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: See Disease
Characteristics No greater than 1 prior chemotherapy regimen (no greater than 7 prior
courses) Endocrine therapy: No concurrent tamoxifen Radiotherapy: Not specified Surgery:
See Disease Characteristics Other: No other concurrent experimental agents

Type of Study:


Study Design:

Allocation: Randomized, Primary Purpose: Treatment

Principal Investigator

William I. Bensinger, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Fred Hutchinson Cancer Research Center


United States: Federal Government

Study ID:




Start Date:

July 1998

Completion Date:

March 2003

Related Keywords:

  • Breast Cancer
  • stage II breast cancer
  • stage IIIA breast cancer
  • Breast Neoplasms



Fred Hutchinson Cancer Research Center Seattle, Washington  98109