A Pilot Trial of Sequential Chemotherapy With Antimetabolite Induction, High-Dose Alkylating Agent Consolidation With Peripheral Blood Progenitor Cell Support, and Intensification With Paclitaxel and Doxorubicin for Patients With High-Risk Breast Cancer
This pilot trial will examine the feasibility of administering induction high-dose therapy
with antimetabolites, followed with consolidation using high-dose single alkylating agent
therapy and finally intensification therapy with sequential cycles of very high doses of the
natural products (paclitaxel followed by doxorubicin) to patients with metastatic breast
cancer (stage IV), and to patients with lesser stage disease at high risk for relapse
(patients with four or more positive nodes (stage II), locally advanced breast cancer (stage
III)), and patients with locally or regionally recurrent breast cancer.
Patients will receive induction therapy with antimetabolite agents (methotrexate, leucovorin
and 5-fluorouracil) for four cycles. Patients will then receive consolidation therapy with
three cycles of high-dose alkylating agents. First, patients will receive one cycle of
high-dose cyclophosphamide administered with growth factor support. PBPCs will be harvested
during the recovery phase of the cyclophosphamide cycle.
The next cycle will consist of high-dose single agent thiotepa. Hematopoietic stem cells
mobilized and collected during the previous cyclophosphamide cycles will be reinfused
following treatment with thiotepa to augment recovery of bone marrow function. After
recovery, intensification with natural product chemotherapy will be administered, consisting
of four cycles of paclitaxel given as a 24-hour infusion followed by four cycles of single
This protocol combines several highly active chemotherapeutic agents in an attempt to
improve upon response rates achieved with current combinations. For high-risk stage II and
III patients, this chemotherapy regimen (without genetic manipulation of PBPCs) will serve
as a chemotherapy backbone onto which a companion immunotherapy protocol will be offered.
An identical chemotherapy regimen will be offered to stage four patients as a backbone for a
trial of retroviral transduction of the MDR1 and NeoR genes into harvested PBPCs.
Endpoint Classification: Safety/Efficacy Study, Primary Purpose: Treatment
United States: Federal Government
|National Cancer Institute (NCI)||Bethesda, Maryland 20892|