Intensive therapy with growth factor support for patients with Ewing tumor metastatic at diagnosis: Pediatric oncology group/children's cancer group phase II study 9457 - A report from the children's oncology group

Mark L. Bernstein*, Meenakshi Devidas, Dominique Lafreniere, Abdul Kader Souid, Paul A. Meyers, Mark Gebhardt, Kimo Stine, Richard Nicholas, Elizabeth J. Perlman, Ronald Dubowy, Irving W. Wainer, Paul S. Dickman, Michael P. Link, Allen Goorin, Holcombe E. Grier

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

84 Scopus citations

Abstract

Purpose: Prognosis is poor for Ewing sarcoma patients with metastasis at diagnosis. We intensified a five-drug therapy (ifosfamide, etoposide alternated with vincristine, doxorubicin, and cyclophosphamide) using filgrastim but not stem-cell support. We studied topotecan alone and combined with cyclophosphamide in therapeutic windows before the five-drug therapy. A randomly assigned proportion of patients received amifostine as a cytoprotective agent. Patients and Methods: Eligible patients were ≤ 30 years old and had histologically proven Ewing sarcoma or primitive neuroectodermal tumor (PNET) and metastasis at diagnosis. Chemotherapeutic cycles began every 21 days, after recovery from toxicities. Results: One hundred ten of the 117 patients enrolled were eligible. Thirty-six patients received initial topotecan. Three had partial responses (PRs), and 17 had progressive disease (PD). Thirty-seven patients were administered topotecan and cyclophosphamide; 21 of these patients achieved PR, and one patient had PD. In a randomly assigned group of 69 patients, amifostine did not provide myeloprotection, which was measured by absolute neutrophil count, platelet count, or cycle intervals. The best responses to the overall therapy included 45 complete responses, 41 PRs, stable disease in 14 patients, and PD in five patients. For all patients, the 2-year event-free survival (EFS) rate was 24% (± 4%), and the overall survival rate was 46% (± 5%). For the 39 patients with isolated pulmonary metastases, the 2-year EFS rate was 31 % (± 7%) compared with 20% (± 5%) for patients with more widespread disease. Conclusion: Topotecan had limited activity in patients with Ewing sarcoma or PNET metastatic at diagnosis. The topotecan-cyclophosphamide combination was active. Amifostine was not myeloprotective. Overall results showed no improvement compared with previous studies.

Original languageEnglish (US)
Pages (from-to)152-159
Number of pages8
JournalJournal of Clinical Oncology
Volume24
Issue number1
DOIs
StatePublished - Jan 1 2006

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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