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Phase II Trial of Sequential High-Dose Alkylating Agents in Metastatic Breast Cancer

Phase 2
18 Years
Not Enrolling
Breast Cancer

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Trial Information

Phase II Trial of Sequential High-Dose Alkylating Agents in Metastatic Breast Cancer

OBJECTIVES: I. Determine the feasibility and efficacy of sequential high-dose
cyclophosphamide, melphalan, and thiotepa plus autologous peripheral blood stem cell rescue
in patients with metastatic breast cancer with ongoing objective response to prior induction

OUTLINE: Patients receive sequential therapy beginning with regimen A. Regimen A: Patients
receive cyclophosphamide IV over 1 hour every 6 hours or more for 4 doses within 36 hours.
Patients receive filgrastim (G-CSF) subcutaneously (SC) daily beginning 2 days after
completion of cyclophosphamide and continuing until autologous peripheral blood stem cells
(PBSC) are harvested. Regimen B: Beginning at least 3 weeks after initiation of regimen A,
patients receive melphalan IV on days 1 and 2. Beginning on day 4, a portion of the PBSC are
reinfused. Patients receive G-CSF SC daily beginning on day 4 and continuing until at least
day 10. Regimen C: Beginning at least 3 weeks after initiation of regimen B, patients
receive thiotepa IV over 2 hours on days 1 and 2. Beginning on day 5, the remaining PBSC are
reinfused. Patients receive G-CSF SC daily beginning on day 5 and continuing until blood
counts recover. During regimens A, B, and C, G-CSF must be discontinued at least 2 days
before administration of any chemotherapy. Regimen D: After recovery from chemotherapy,
patients with hormone receptor-positive tumors and no prior refractoriness to hormonal
therapies receive oral tamoxifen daily, while patients with prior failure on tamoxifen
receive oral megestrol 4 times daily. Patients undergo irradiation to sites of prior
cutaneous, nodal, bone, or soft tissue bulk disease and resection of residual lesions.
Patients are followed weekly for 1 month, biweekly for 2 months, monthly for 5 months, and
then bimonthly for 1 year.

PROJECTED ACCRUAL: A minimum of 30 patients will be accrued for this study.

Inclusion Criteria

DISEASE CHARACTERISTICS: Histologically proven stage IV breast carcinoma that is
considered incurable by standard treatment Ongoing objective response to prior induction
chemotherapy required No brain metastasis Hormone receptor status: Estrogen and
progesterone receptor status known

PATIENT CHARACTERISTICS: Age: Over 18 Sex: Not specified Menopausal status: Not specified
Performance status: Karnofsky 90-100% Life expectancy: More than 3 months Hematopoietic:
Absolute neutrophil count greater than 1,500/mm3 Platelet count greater than 100,000/mm3
Hemoglobin greater than 9 g/dL Hepatic: Bilirubin less than 1.5 times upper limit of
normal (unless due to benign congenital hyperbilirubinemia) PT and aPTT normal Liver
biopsy normal if serologic evidence of active hepatitis B or C Renal: Creatinine no
greater than 1.2 mg/dL Cardiovascular: No active heart disease LVEF at least 50% and no
abnormal wall motion by MUGA scan Pulmonary: DLCO normal Other: Nutritional status
adequate (more than 1,000 calories/day orally) HIV negative No other active serious
medical or psychiatric disease No other prior malignancy except basal cell skin cancer or
carcinoma in situ of the cervix uteri Not pregnant Negative pregnancy test Fertile
patients must use effective barrier contraception during and for up to 2 years after study

PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: No prior mitomycin
or nitrosourea No prior anthracycline greater than 500/m2 unless previously received
dexrazoxane At least 4 weeks since other prior chemotherapy Endocrine therapy: Not
specified Radiotherapy: No prior radiotherapy to pelvis or brain Surgery: At least 2 weeks
since prior major surgery

Type of Study:


Study Design:

Primary Purpose: Treatment

Principal Investigator

Michael DiGiovanna, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Yale University


United States: Federal Government

Study ID:




Start Date:

February 1994

Completion Date:

December 2000

Related Keywords:

  • Breast Cancer
  • stage IV breast cancer
  • recurrent breast cancer
  • Breast Neoplasms



Yale Comprehensive Cancer Center New Haven, Connecticut  06520-8028