Induction of apoptosis by topotecan: implications for the treatment of leukemia

Topotecan is a topoisomerase I inhibitor with activity against acute leukemia. Two phase I studies using infusional topotecan as a single agent demonstrated that the dose-limiting toxicity of topotecan in hematologic malignancies is mucositis; similar toxicity was observed in a phase I study of topotecan in combination with cytarabine. In the latter study, the percentage of bone marrow cells in S-phase correlated with response to therapy. Further studies of topotecan-based regimens in acute leukemia are indicated.