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Phase I-II Study of Dose Intense Doxorubicin, Paclitaxel And Cyclophosphamide With Peripheral Blood Progenitor Cells (PBPC) And Cytokine Support In Patients With Metastatic Breast Cancer

Phase 1/Phase 2
15 Years
60 Years
Not Enrolling
Breast Cancer

Thank you

Trial Information

Phase I-II Study of Dose Intense Doxorubicin, Paclitaxel And Cyclophosphamide With Peripheral Blood Progenitor Cells (PBPC) And Cytokine Support In Patients With Metastatic Breast Cancer

OBJECTIVES: I. Define the maximum tolerated doses of four courses of doxorubicin (DOX),
paclitaxel (TAX), and cyclophosphamide (CTX) followed by peripheral blood stem cell (PBSC)
and granulocyte colony-stimulating factor support given in an out-patient setting in
patients with metastatic breast cancer. II. Evaluate the cardiotoxicity of the combination
of bolus DOX, a 3-hour infusion of TAX, and CTX. III. Determine the clinical response rate
and time to progression associated with this regimen. IV. Determine Cmax, AUC and the
drug:metabolite ratio of TAX and DOX when given with CTX, a known p450 inducer.

OUTLINE: Patients without prior doxorubicin (DOX) or paclitaxel (TAX) receive two courses of
induction chemotherapy with DOX/TAX with G-CSF support given 3 weeks apart. Peripheral blood
stem cells (PBSC) are harvested during the recovery phase following the second course.
Patients who previous received DOX or TAX and responded receive cyclophosphamide (CTX) with
G-CSF for stem cell mobilization followed by PBSC harvest. Back-up bone marrow may be
harvested from patients without marrow involvement for whom PBSC collection is inadequate.
Patients with responding or stable disease who have adequate PBSC available receive
dose-intensive chemotherapy with DOX, CTX, and TAX given on day 1, with PBSC infused on day
3 and G-CSF given from day 3 until neutrophil recovery. Four courses of dose-intensive
chemotherapy with PBSC and G-CSF support are given every 3-4 weeks. During the phase I
portion of the study, groups of 3-6 patients are treated at increasing doses of DOX, TAX,
and CTX until the maximum tolerated dose (MTD) is determined; during the phase II portion,
additional patients are treated at the MTD. Patients who progress after 2 courses of
induction or 2 courses of dose-intensive chemotherapy are given the option of receiving
their PBSC after conditioning with a different regimen (e.g., CTX, etoposide, and
cisplatin). Patients who receive induction on protocol but who choose not to receive
dose-intensive chemotherapy continue DOX/TAX for a total of 6 courses. Patients are followed
3, 6, 12, 18, and 24 months after therapy, then as clinically indicated.

PROJECTED ACCRUAL: During the phase I portion of the study, groups of 3-6 patients will be
entered at each dose level studied. During the phase II portion of the study, 25 patients
will be treated at the maximum tolerated dose.

Inclusion Criteria

DISEASE CHARACTERISTICS: Histologically confirmed breast cancer that is metastatic or
recurrent Poor-prognosis status required for Phase I portion of the study, i.e.: Estrogen
receptor and progesterone receptor-negative tumor OR Failed hormonal therapy and with
bulky disease or liver metastasis Bone marrow involvement less than 15% No active CNS

PATIENT CHARACTERISTICS: Age: 15 to 60 Sex: Not specified Performance status: Zubrod 0 or
1 Hematopoietic: WBC greater than 3,500/mm3 Absolute granulocyte count greater than
2,000/mm3 Platelet count greater than 100,000/mm3 Hepatic: Liver function tests less than
twice normal Renal: Creatinine clearance (calculated) at least 60 mL/min Cardiovascular:
Left ventricular ejection fraction greater than 50% No symptomatic cardiac disease
requiring antiarrhythmic or inotropic therapy Pulmonary: DLCO greater than 50% of
predicted Other: No pre-existing peripheral neuropathy greater than grade 1 No severe
concomitant medical or psychiatric disease

PRIOR CONCURRENT THERAPY: Biologic therapy: More than 3 weeks since any immunotherapy
Chemotherapy: No prior doxorubicin or paclitaxel Patients with up to 150 mg per square
meter doxorubicin or up to 4 courses of paclitaxel and who have responding disease are
eligible for dose-intensive portion of protocol therapy Endocrine therapy: Not specified
Radiotherapy: More than 3 weeks since any radiotherapy Surgery: Not specified

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum Tolerated Doses (MTD) of 4 courses Doxorubicin, Paclitaxel, + Cyclophosphamide followed by PBSC and G-CSF Support

Outcome Time Frame:

Evaluated with each 3-4 week course

Safety Issue:


Principal Investigator

Michele L. Donato, MD

Investigator Role:

Study Chair

Investigator Affiliation:

M.D. Anderson Cancer Center


United States: Federal Government

Study ID:




Start Date:

September 1995

Completion Date:

January 2002

Related Keywords:

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



University of Texas - MD Anderson Cancer Center Houston, Texas  77030-4009