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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

From the Department of Pediatrics, Boston Floating Hospital for Infants and Children, Boston, MA; Department of Hematology/Oncology, Children's Memorial Medical Center at Chicago, Chicago, IL; Department of Radiation Oncology, Midwest Children's Cancer Center, Milwaukee, WI; Department of Pathology, Hospital for Sick Children, Toronto, Ontario, Canada; Department of Pathology and Laboratory Medicine, Hartford Hospital, Hartford, CT; Department of Radiation Oncology, Children's Healthcare of Atlanta at Egleston, Atlanta, GA; Department of Surgery, University of Texas Southwestern, Dallas, TX; Children's Oncology Group Statistics Department, University of Florida, Gainesville, FL; and the Department of Pediatric Hematology/Oncology, University of Alabama, Birmingham, AL

Address reprint requests to Cynthia S. Kretschmar, MD, Boston Floating Hospital for Infants and Children, Department of Pediatrics, Division of Pediatric Oncology, 750 Washington St, Box 14, Boston, MA 02111; e-mail: ckretschmar{at}tufts-nemc.org

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.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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