Response to Paclitaxel, Topotecan, and Topotecan-Cyclophosphamide in Children With Untreated Disseminated Neuroblastoma Treated in an Upfront Phase II Investigational Window: A Pediatric Oncology Group Study

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Abstract
Purpose Most children older than 1 year of age with metastatic neuroblastoma (NB) die despite intensive chemotherapy and bone marrow transplantation. The Pediatric Oncology Group conducted a study of paclitaxel, topotecan, and topotecan-cyclophosphamide (topo-cyclo) in newly diagnosed children with stage IV NB. Patients and Methods There were 102 patients enrolled between September 1993 and October 1995; two of them were later shown to be ineligible. Of the remaining 100 patients, the first cohort of 33 patients received paclitaxel 350 mg/m2 intravenously (IV) over 24 hours every 14 to 21 days; the next 33 patients received topotecan 2 mg/m2/d for 5 days IV every 21 days; a third cohort of 34 patients were treated with IV cyclophosphamide 250 mg/m2 followed by topotecan 0.75 mg/m2 each day for 5 days every 21 days. Patients were re-evaluated after two courses and then treated with intensive induction therapy and bone marrow transplantation. Results Objective responses (complete response + partial response + mixed response) were documented in 67% of children who received topotecan, 76% after topo-cyclo, and 25% after paclitaxel. Four patients had grade 3 to 4 allergic reactions to paclitaxel; most patients developed grade 3 to 4 marrow suppression after topotecan or topo-cyclo. Neither disease-free survival nor overall survival differed significantly between children who received a phase II agent and those who did not. The 6-year disease-free survival and overall survival rates for all 100 children were 18% ± 5% and 26% ± 5%, respectively. Conclusion Topotecan and topo-cyclo are active in children with NB, are well tolerated, and should be evaluated further in combination regimens.

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