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

Cynthia S. Kretschmar*, Morris Kletzel, Kevin Murray, Paul Thorner, Vijay Joshi, Robert Marcus, E. Ide Smith, Wendy B. London, Robert Castleberry

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

59 Scopus citations

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/m 2 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.

Original languageEnglish (US)
Pages (from-to)4119-4126
Number of pages8
JournalJournal of Clinical Oncology
Volume22
Issue number20
DOIs
StatePublished - 2004

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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