Phase I study of Topotecan, a new topoisomerase I inhibitor, in patients with refractory or relapsed acute leukemia

摘要: The purpose of this study was to define, in a phase I leukemia, the maximally tolerated dose (MTD), major toxicities, and possible antitumor activity Topotecan, new topoisomerase (topo I) inhibitor. Topotecan delivered by 5-day continuous infusion every 3 4 weeks patients with refractory or relapsed acute at doses ranging from 3.5 mg/m2 18 per course. Twenty-seven were treated, including 17 myelogenous undifferentiated 7 lymphocytic chronic leukemia blastic phase. Severe mucositis dose-limiting toxicity occurring two five treated 11.8 course; third patient had prolonged myelosuppression. At MTD 10 course, 1 12 severe 5 mild-to- moderate mucositis. Nausea, vomiting, diarrhea, myelosuppression uncommon. Three (11%) achieved complete response, (7%) partial one (4%) hematologic improvement. overall plus response rate 19%, 24% leukemia. A novel vitro assay that quantifies Topotecan-stabilized topo I-DNA complexes samples used, which demonstrated heterogeneity ability interact I, intracellular target Topotecan. This defined be over days toxicity. Future studies will define precise different subsets, its efficacy combination other antileukemic drugs, correlations between Topotecan-induced complex formation individual