Chemotherapy in Treating Children With Recurrent or Refractory Sarcomas

OBJECTIVES:

I. Determine the response rate in children with recurrent or refractory brain tumors, sarcomas, or neuroblastomas treated with topotecan. (Brain tumor and neuroblastoma strata closed to accrual effective 07/02/2001) II. Assess the toxicity of this regimen in a larger group of patients treated at the currently defined maximum tolerated dose.

OUTLINE: This is a multicenter study.

Patients receive topotecan IV continuously on days 1-21. Treatment continues at least every 4 weeks in the absence of unacceptable toxicity or disease progression.

Patients are followed every 3 months.

DISEASE CHARACTERISTICS:

• Histologically confirmed malignancy that is relapsed or refractory to conventional therapy at original diagnosis including:

• Brain tumors

• Gliomas or astrocytomas
• Medulloblastomas or primitive neuroectodermal tumor (PNET) in CNS
• (Brain tumor stratum closed to accrual effective 07/02/2001)
• Sarcomas

• Soft tissue sarcoma (undifferentiated sarcoma, embryonal or alveolar rhabdomyosarcoma (RMS), or non-RMS soft tissue sarcoma)
• Osteosarcoma
• Ewing's sarcoma/peripheral PNET tumors
• Neuroblastoma

• (Neuroblastoma stratum closed to accrual effective 07/02/2001)
• Histology requirement waived for brain stem tumors (Brain tumor stratum closed to accrual effective 07/02/2001)
• Measurable disease documented by clinical, radiographic, or histologic criteria
• Lesions in previously irradiated fields may be used to assess tumor response if there has been evidence of subsequent tumor growth in those fields
• No bone marrow metastases with granulocytopenia and/or thrombocytopenia

PATIENT CHARACTERISTICS:

Age:

• 30 days to 21 years at diagnosis

Performance status:

• ECOG 0-2

Life expectancy:

• More than 2 months

Hematopoietic:

• Absolute neutrophil count at least 1,000/mm3
• Hemoglobin at least 10.0 g/dL (may receive RBC transfusions)
• Platelet count at least 100,000/mm3 (50,000/mm3 if post bone marrow transplantation) (transfusion independent)

Hepatic:

• Bilirubin no greater than 1.5 times normal
• SGOT or SGPT less than 2.5 times normal

Renal:

• Creatinine no greater than 1.5 times normal OR
• Creatinine clearance or radioisotope glomerular filtration rate at least 70 mL/min

Neurologic:

• No greater than grade 2 CNS toxicity OR
• Stable CNS status for brain tumors (Brain tumor stratum closed to accrual effective 07/02/2001)
• Seizure disorders allowed if well-controlled with anticonvulsants

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• At least 3 months since prior bone marrow transplantation and recovered
• At least 2 weeks since prior cytokines and recovered
• No concurrent filgrastim (G-CSF) or other cytokines
• No concurrent immunomodulating agents

Chemotherapy:

• At least 2 weeks since prior chemotherapy (4 weeks for nitrosoureas) and recovered
• No prior topotecan or other camptothecins
• No other concurrent anticancer chemotherapy

Endocrine therapy:

• Concurrent corticosteroids for CNS tumors with increased intracranial pressure allowed (Brain tumor stratum closed to accrual effective 07/02/2001)

Radiotherapy:

• At least 2 months since prior craniospinal radiotherapy or radiotherapy to more than 50% of the bone marrow and recovered
• Concurrent radiotherapy to localized painful lesions allowed provided that at least 1 measurable lesion is not irradiated

Other:

• Recovered from any other prior therapy