title: 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.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  Eligible patients were < or = 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Hôpital Sainte-Justine, Hematology Oncology, Montréal Québec, Canada. bernstm@magellan.umontreal.ca
authors.forename: Mark L
authors.initials: ML
authors.lastname: Bernstein
authors.forename: Meenakshi
authors.initials: M
authors.lastname: Devidas
authors.forename: Dominique
authors.initials: D
authors.lastname: Lafreniere
authors.forename: Abdul-Kader
authors.initials: AK
authors.lastname: Souid
authors.forename: Paul A
authors.initials: PA
authors.lastname: Meyers
authors.forename: Mark
authors.initials: M
authors.lastname: Gebhardt
authors.forename: Kimo
authors.initials: K
authors.lastname: Stine
authors.forename: Richard
authors.initials: R
authors.lastname: Nicholas
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Perlman
authors.forename: Ronald
authors.initials: R
authors.lastname: Dubowy
authors.forename: Irving W
authors.initials: IW
authors.lastname: Wainer
authors.forename: Paul S
authors.initials: PS
authors.lastname: Dickman
authors.forename: Michael P
authors.initials: MP
authors.lastname: Link
authors.forename: Allen
authors.initials: A
authors.lastname: Goorin
authors.forename: Holcombe E
authors.initials: HE
authors.lastname: Grier
mesh_terms: D000293:Adolescent; D000328:Adult; D004999:Amifostine / Q000009:adverse effects / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000401:mortality; D002648:Child; D002675:Child, Preschool; D003520:Cyclophosphamide / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006801:Humans; D008297:Male; D012512:Sarcoma, Ewing / Q000188:drug therapy* / Q000401:mortality; D019772:Topotecan / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D019772:Topotecan; D003520:Cyclophosphamide; D004999:Amifostine