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.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum Tolerated Doses (MTD) of 4 courses Doxorubicin, Paclitaxel, + Cyclophosphamide followed by PBSC and G-CSF Support
Evaluated with each 3-4 week course
Michele L. Donato, MD
M.D. Anderson Cancer Center
United States: Federal Government
|University of Texas - MD Anderson Cancer Center||Houston, Texas 77030-4009|