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
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
Stage III patients may begin therapy prior to or following surgery. Patients with undrainable
 significant third space fluid collection (e.g., pleural effusions, ascites) are entered
 directly on Consolidation.

 Patients receive induction chemotherapy with methotrexate and fluorouracil every 2 weeks for
 4 courses.

 Patients then receive two 3-week courses of consolidation therapy with cyclophosphamide,
 followed by daily granulocyte colony-stimulating factor until completion of leukapheresis.
 Patients next receive myeloablative doses of thiotepa followed by stem cell rescue and
 granulocyte colony-stimulating factor.

 After hematopoietic reconstitution, patients receive 24-hour infusions of paclitaxel every 3
 weeks for 4 doses, followed by doxorubicin or vinblastine every 3 weeks for 4 doses. Patients
 are then evaluated for additional therapy (surgery, radiotherapy, or hormonal therapy) as
 appropriate.

 Patients are followed every 3 months for 1 year, then every 6 months.
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
 agent doxorubicin.

 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.
DISEASE CHARACTERISTICS:

 Histologically proven AR and ESFT which includes: Classical, atypical and extraosseous
 Ewing's sarcoma, primitive peripheral neuroectodermal tumors, peripheral neuroepithelioma,
 primitive sarcoma of bone, and ectomesenchymoma.

 Confirmed presence of tumor-specific infusion protein by documented RT-PCR which
 corresponds to one of the tumor specific peptides available for vaccination.

 Measurable tumor.

 No prior or current CNS metastases.

 PRIOR/CONCURRENT THERAPY:

 ARM A PATIENTS:

 May be enrolled on the protocol for the first phase in the absence of RT PCR documentation
 of a tumor-specific fusion protein which corresponds to one of the tumor-specific peptides
 available for vaccination. However, RT PCR documentation at the time of tumor recurrence
 must occur prior to administration of immunotherapy. At time of initial tumor diagnosis,
 prior to any cytoreductive therapy.

 ARM B PATIENTS:

 Tumor recurrence occurring during or after receiving at least first line cytoreductive
 therapy for ESFT and AR. No more than two post-recurrence salvage regimens unless
 peripheral CD4+T cell number is greater than 400 cells per millimeter cubed.

 At least 6 weeks since any treatments and recovered from all acute toxic effects from time
 in which immunotherapy will be started for this study.

 No concurrent estrogen therapy during immunotherapy section of study.

 PATIENT CHARACTERISTICS:

 Age: 2-25 (at time of initial diagnosis of alveolar rhabdomyosarcoma).

 Weight: Greater than 15 kg (at time of apheresis).

 Performance status: ECOG 0-2.

 Life expectancy: At least 8 weeks.

 Hematopoietic:

 ANC greater than 100,000/mm(3).

 Hemoglobin greater than 9.0 g/dL.

 Platelet count greater than 50,000/mm(3).

 Hepatic:

 Bilirubin less than 2.0 mg/dL (unless related to involvement by tumor).

 Transaminases less than 3 times normal (unless related to involvement by tumor).

 Renal:

 Creatinine less than 1.5 mg/dL or creatinine clearance greater than 60 mL/min.

 Cardiovascular:

 No major disorder of cardiovascular system.

 Cardiac ejection fraction greater than 40%.

 Pulmonary:

 No major disorder of pulmonary system.

 OTHER:

 Not pregnant or nursing.

 HIV negative.

 Hepatitis B or C negative.

 No patients requiring daily oral corticosteroid therapy.

 If allergic to eggs, egg products, or thimerosal, or have a history of Guillain-Barre
 syndrome, ineligible to receive influenza vaccine.