A Phase I Pharmacokinetic Optimal Dosing Study of Intraventricular Topotecan for Children With Neoplastic Meningitis

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Diagnosis of neoplastic meningitis secondary to leukemia, lymphoma (including
AIDS-related lymphoma), or solid tumor (including primary CNS tumors or carcinomas of
unknown primary site), defined by 1 of the following criteria:

- Cerebral spinal fluid (CSF) cell count > 5/μL AND evidence of blast cells on
cytospin or by cytology (for patients with leukemia or lymphoma)

- Presence of tumor cells on cytospin or cytology OR unequivocal presence of
meningeal disease by MRI (for patients with solid tumor)

- No conventional therapy for neoplastic meningitis exists

- Patients with CNS leukemia or lymphoma must be refractory to conventional
therapy, including radiotherapy (i.e., second or greater relapse)

- Patients with CNS leukemia or lymphoma must have had a negative bone marrow
aspiration within the past 2 weeks

- No clinical evidence of obstructive hydrocephalus

- No compartmentalization of CSF flow by radioisotope indium In 111 or technetium Tc 99
DTPA flow study

- No ventriculoperitoneal or ventriculoatrial shunt unless patient is completely
shunt-independent

- No impending spinal cord compression or other CNS involvement (e.g., acute visual
loss secondary to optic nerve involvement) requiring emergent local radiotherapy

PATIENT CHARACTERISTICS:

Age

- 3 to 21

Performance status

- Lansky 60-100% (≤ 16 years of age) OR

- Karnofsky 60-100% (> 16 years of age)

Life expectancy

- Not specified

Hematopoietic

- Not specified

Hepatic

- Not specified

Renal

- Calcium ≥ 7 mg/dL

Other

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- Sodium 125-150 mmol/L

- Magnesium ≥ 0.7 mmol/L

- Must have or be willing to have an intraventricular access device (i.e., Ommaya
reservoir)

- No uncontrolled infection

- HIV-positive patients with AIDS-related lymphomatous meningitis are eligible

- No other significant uncontrolled systemic medical illness that would preclude study
participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

- Recovered from prior biologic therapy or immunotherapy

Chemotherapy

- Recovered from prior chemotherapy

- At least 1 week since prior intra-colony stimulating factory (CSF) chemotherapy (2
weeks for liposomal cytarabine)

- At least 3 weeks since prior systemic chemotherapy for leptomeningeal disease

- Concurrent systemic chemotherapy to control systemic disease or bulk CNS disease
allowed provided the systemic chemotherapy is not an investigational agent OR any of
the following:

- High-dose (> 1 g/m^2) methotrexate

- High-dose (> 1 g/m^2) cytarabine

- Fluorouracil

- Capecitabine

- Thiotepa

- Nitrosoureas

- Topotecan

Endocrine therapy

- Not specified

Radiotherapy

- See Disease Characteristics

- At least 8 weeks since prior craniospinal radiotherapy and recovered

- No concurrent CNS radiotherapy

- Concurrent radiotherapy to extra-CNS sites (e.g., painful bone metastases not in
the craniospinal axis) allowed

Surgery

- Not specified

Other

- More than 2 weeks since prior and no other concurrent investigational agents

- No other concurrent intra-CSF or systemic therapy for leptomeningeal disease