Combination Chemotherapy and Peripheral Stem Cell Transplantation in Treating Patients With Sarcoma

OBJECTIVES: I. Determine the feasibility of sequential high-dose chemotherapy with
ifosfamide and doxorubicin followed by melphalan and cisplatin, each followed by autologous
peripheral blood stem cell support, in patients with high-risk or advanced sarcomas. II.
Determine the toxic effects of this regimen in these patients. III. Determine response rate
and disease-free and overall survival in these patients treated with this regimen.

OUTLINE: Beginning at least 4 weeks prior to the start of chemotherapy, patients receive
filgrastim (G-CSF) subcutaneously daily until the completion of peripheral blood stem cell
(PBSC) harvesting. Beginning 5 days after the start of G-CSF, PBSCs are collected over
several days. Patients who do not mobilize sufficient cells undergo bone marrow harvest.
Regimen A: Patients receive high-dose ifosfamide IV and doxorubicin IV continuously over 96
hours on days -8 to -4. 12.5% of PBSCs or bone marrow are reinfused on day -2 and 37.5% are
reinfused on day 0. Patients receive G-CSF IV beginning on day 0 and continuing until blood
counts recover. Regimen B: Beginning at least 4 weeks after day 1 of Regimen A, patients
receive high-dose melphalan IV followed immediately by cisplatin IV on days -11 and -4.
Patients receive G-CSF IV on days -10 to -6. 12.5% of PBSCs or bone marrow are reinfused on
day -3 and the remaining 37.5% are reinfused on day 0. Patients receive G-CSF IV beginning
on day 0 and continuing until blood counts recover. Patients are followed monthly for 1
year, every 3 months for 1 year, and then as needed for 3 years.

PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study within 3 years.

DISEASE CHARACTERISTICS: Histologically confirmed sarcomas in the following categories:
Soft tissue sarcoma (STS) High-grade STS of the extremities Primary extending to fascia or
locally recurrent At least 10 cm in greatest dimension or multifocal on surgical pathology
Primary site controlled by surgery and/or radiotherapy High-grade truncal or head and neck
sarcoma At least 10 cm in greatest dimension or any size with no surgical options for
clear margins Primary site controlled by surgery and/or radiotherapy Locally recurrent
disease in CR or PR after surgery, chemotherapy, or radiotherapy Metastatic STS in CR or
PR after surgery, chemotherapy, or radiotherapy Osteosarcoma (OS) Extremity OS after
neoadjuvant chemotherapy and surgical resection provided: Less than 50% necrosis in the
surgical specimen LDH or alkaline phosphatase greater than 2 times normal at presentation
Axial OS in CR or PR after chemotherapy and/or surgery Primary or recurrent metastatic OS
in CR or PR after chemotherapy, surgery, and/or radiotherapy Ewing's sarcoma or primitive
neuroectodermal tumor Primary site in CR or PR after chemotherapy, radiotherapy, or
surgery Rib, pelvic, or axial skeleton primary Bulky tumor (at least 10 cm in greatest
diameter) Primary or recurrent metastatic disease in CR or PR after surgery, chemotherapy,
or radiotherapy Rhabdomyosarcoma Gross residual disease after primary treatment with
surgery, chemotherapy, and radiotherapy Primary group IV or recurrent metastatic disease
in CR or PR after chemotherapy and radiotherapy with or without surgery No brain
metastasis No histologically confirmed bone marrow metastasis Prior metastases allowed
with clearing of bone marrow at entry No contraindication to collection of mobilized stem
cells or, if needed, autologous bone marrow

PATIENT CHARACTERISTICS: Age: 10 to 55 Performance status: Karnofsky 80-100%
Hematopoietic: Absolute neutrophil count greater than 2,000/mm3 Platelet count greater
than 150,000/mm3 Hemoglobin greater than 10 g/dL Hepatic: See Disease Characteristics
Bilirubin less than 1.5 mg/dL AST and ALT less than 3 times normal Hepatitis B surface
antigen negative Negative hepatitis C antigen test required in patients with hepatitis C
antibody Renal: Creatinine less than 1.4 mg/dL Creatinine clearance greater than 75 mL/min
Cardiovascular: LVEF at least 55% by MUGA or echocardiogram No history of significant
cardiac disease Pulmonary: FEV1 greater than 2 liters PaO2 greater than 70 mm Hg on room
air PaCO2 less than 42 mm Hg on room air DLCO greater than 60% predicted Other: No hearing
loss of greater than 40 decibels HIV negative No organic or psychiatric CNS dysfunction
that would preclude study No other medical or psychosocial problems that would place
patient at unacceptable risk No history of other malignancy except nonmelanoma skin cancer
or carcinoma in situ of the cervix Not pregnant Negative pregnancy test Fertile patients
must use effective contraception

PRIOR CONCURRENT THERAPY: More than 2 weeks since treatment to control primary or
recurrent tumor Biologic therapy: Not specified Chemotherapy: See Disease Characteristics
No more than 2 prior chemotherapy regimens (including adjuvant therapy) Prior cumulative
cisplatin dose less than 400 mg/m2 Prior cumulative doxorubicin dose less than 240 mg/m2
Endocrine therapy: Not specified Radiotherapy: See Disease Characteristics No prior
radiotherapy to more than 20% of the bone marrow-containing axial skeleton No prior
radiotherapy to the left chest wall Surgery: See Disease Characteristics