There is currently no established therapy for MDS. Recently, a single center, non-randomized clinical trial using topotecan 2 mg/m2 ) in 47 patients with MDS (RAEB, RAEB-t, or CMML) demonstrated complete responses in 13 patients (28%) and partial responses in six patients (13%). However, this regimen was associated with significant toxicity, including death in eight patients. In this study, we propose to administer a dose of topotecan to patients with MDS using a six hour infusion regimen that can be easily delivered in an outpatient setting. The vast majority of patients with MDS and excess blasts when treated with the standard induction chemotherapy for AML either do not survive or fail to improve. In contrast, a significant yet small proportion of patients with MDS and excess blasts achieve a significant improvement with small doses of cytosar which are not effective for AML. Thus, we hope that a less toxic dose of topotecan still may be effective this clinical entity. Since the pharmacokinetics of topotecan administration in patients with MDS is unknown, we will analyze concentrations of topotecan and its metabolites and topoisomerase I/DNA complexes to provide a basis for optimizing the dose of topotecan in this disease.
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