A Phase I/II Study of Topotecan With G-CSF and Radiation Therapy in Children With Malignant Intrinsic Pontine Brainstem Gliomas of Childhood

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Diagnosis of intrinsic pontine brain stem glioma within the past 30 days

- Histologic confirmation not required provided the tumor has a pontine epicenter
AND exhibits diffuse (rather than focal) involvement of ≥ 2/3 of the pons with
or without extension to the adjacent medulla or midbrain* NOTE: *Brain stem
tumors that do not meet these criteria must be histologically confirmed as grade
III or IV malignant glioma

- Measurable disease by radiographic imaging

- Post-operative MRI required within the past 30 days if patient had a biopsy or
surgical resection

- No disseminated disease

- No neurofibromatosis type 1

PATIENT CHARACTERISTICS:

Age

- 3 to 21 at diagnosis

Performance status

- Lansky 50-100% OR

- Karnofsky 50-100%

Life expectancy

- At least 8 weeks

Hematopoietic

- Absolute neutrophil count ≥ 1,000/mm^3

- Platelet count ≥ 100,000/mm^3 (transfusion independent)

- Hemoglobin ≥ 10.0 g/dL (transfusion allowed)

Hepatic

- Bilirubin ≤ 1.5 times upper limit of normal (ULN)

- ALT < 2.5 times ULN

Renal

- Creatinine clearance or radioisotope glomerular filtration rate ≥ 70 mL/min OR

- Creatinine based on age as follows:

- No greater than 0.8 mg/dL (for patients ≤ 5 years of age)

- No greater than 1.0 mg/dL (for patients 6 to 10 years of age)

- No greater than 1.2 mg/dL (for patients 11 to 15 years of age)

- No greater than 1.5 mg/dL (for patients over 15 years of age)

Other

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- Not severely somnolent or comatose

- Central cortical neurotoxicity scale < grade 3

PRIOR CONCURRENT THERAPY:

Biologic therapy

- No concurrent immunomodulating agents

Chemotherapy

- No other concurrent anticancer chemotherapy

Endocrine therapy

- Concurrent corticosteroids allowed for neurological deficits related to the tumor

Radiotherapy

- No prior radiotherapy

Surgery

- See Disease Characteristics

- Prior biopsy or surgical resection for malignant brain stem glioma allowed

Other

- No other prior therapy for malignant brain stem glioma