ARTICLE Relationship Between Topotecan Systemic Exposure and Tumor Response in Human Neuroblastoma

Background: Topotecan is a topoisomerase I inhibitor with activity against xenografts of childhood solid tumors and established clinical activity against neuroblastoma and rhab-domyosarcoma. We have studied the relationship between systemic exposure to and the antitumor activity of topotecan lactone (the active form of the drug) in the xenograft models. Furthermore, we determined whether the responses seen in these models occur at systemic exposure levels that are tol-erable in children. Methods: Neuroblastoma xenografts de-rived from the tumors of six different patients were estab-lished subcutaneously in immune-deprived mice. Topotecan was administered by intravenous bolus injection 5 days a week for 2 consecutive weeks, repeated every 21 days for three cycles. The minimum daily doses that induced com-plete responses (CRs) and partial responses (PRs) were de