This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Hypothesis: Intrathecal topotecan will have anti-tumor activity in children with neoplastic meningitis.
Specific Aims : Primary Objectives 1. To estimate the MTD of intraventricular topotecan administered daily for 5 consecutive days. 2. To describe the toxicities and define the dose-limiting toxicity of topotecan following intraventricular administration daily for 5 consecutive days. 3. To determine if the MTD of intraventricular topotecan is also a pharmacokinetic optimal dose as defined by topotecan lactone concentrations in the cerebral CSF. Secondary Objectives 1. To provide preliminary descriptions of the anti-tumor activity of intraventricular topotecan observed in the heterogeneous diseases that will be treated in this trial. 2. To investigate MMP, VEGF, and other potential biological markers in the CSF of patients with neoplastic meningitis prior to and throughout treatment with intraventricular topotecan. 3. To further describe the CSF pharmacokinetics of topotecan following CSF administration. 4. To investigate the feasibility of central review imaging following treatment and to correlate observed effects with response to intraventricular therapy.
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