Therapy for Children With Advanced Stage High Risk Neuroblastoma

In this prospective phase II trial, topotecan is administered intravenously daily for 5 days for each of 2 consecutive weeks for two cycles in an upfront treatment window. Patients subsequently will receive standard treatment during induction and intensification phases.

The objectives of this trial are:

• To estimate the response rate to an upfront window of two cycles of IV topotecan when given in doses adjusted to attain a targeted systemic exposure in children with advanced stage neuroblastoma.
• To determine the feasibility and toxicity of an intensification phase of high-dose chemotherapy with topotecan and cyclophosphamide followed by autologous peripheral blood stem cell transplant
• To estimate the 3-year overall survival and progression-free survival in patients treated with this approach
• To characterize the phenotype of neuroblastoma tumor cells
• To evaluate the disposition of topotecan in previously untreated patients with neuroblastoma

Details for chemotherapy intervention:

Window Phase Topotecan description, window therapy-Topotecan given intravenously daily as a 30 minute infusion for five consecutive days, off two days, and then five consecutive days. The dose for day 1 and 2 was 3.0 mg/m2 and subsequent doses were adjusted to attain a target systemic exposure. A second course of Topotecan was given approximately 16 days from the end of the first cycle, with the initial dose for the second course of Topotecan based on the dose required in the preceding course to attain the target AUC.