Chemotherapy and Stem Cell Transplantation in Treating Children With Central Nervous System Cancer

OBJECTIVES:

• Determine the feasibility of administering an outpatient protocol comprising high-dose carboplatin with autologous stem cell support and etoposide in pediatric patients with primary central nervous system malignancies.
• Determine the maximum tolerated dose of carboplatin when administered in this regimen in these patients.
• Determine the toxicity of this regimen in these patients.

OUTLINE: This is dose-escalation study of carboplatin.

Patients receive filgrastim (G-CSF) IV once daily for 6 days followed by a maximum of 5 apheresis sessions. If the target number of peripheral blood stem cells is not achieved, some patients receive G-CSF and undergo apheresis as above after a 2-week rest.

At least 3 days after completion of G-CSF, patients receive high-dose carboplatin IV over 1 hour on day 1, stem cell reinfusion on day 3, G-CSF subcutaneously on days 4-18 and 43-61, and oral etoposide 3 times daily on days 21-42. Treatment continues for a maximum of 4 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of carboplatin until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Patients are followed monthly for 1 year and then annually thereafter.

PROJECTED ACCRUAL: A total of 3-15 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically confirmed primary central nervous system malignancy
• Recurrent, persistent, or progressive disease after at least 1 prior first-line treatment regimen

PATIENT CHARACTERISTICS:

Age

• 18 and under at initial diagnosis

Performance status

• ECOG 0-2

Life expectancy

• At least 8 weeks

Hematopoietic

• Absolute neutrophil count greater than 750/mm^3
• WBC greater than 2,500/mm^3
• Platelet count greater than 100,000/mm^3
• No underlying myelodysplasia, stem cell disorder, or other inherent hematologic synthetic defect

Hepatic

• Liver function tests less than 2 times normal OR
• Absence of active hepatitis by liver biopsy
• Bilirubin less than 1.5 mg/dL

Renal

• Glomerular filtration rate greater than 60 mL/min by radionucleotide assay

Cardiovascular

• Ejection fraction at least 45%

Pulmonary

• Clinically normal pulmonary function (patients 5 years of age and under)
• FEV_1 and FVC at least 50% (patients over 5 years of age) OR
• Arterial blood gas normal and DLCO greater than 50%

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No mucositis or mucosal infection
• HIV negative

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• At least 3 weeks since prior systemic cytotoxic chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• At least 6 months since prior radiotherapy to the pelvis or spine

Surgery

• Not specified