title: Treatment of metastatic Ewing sarcoma/primitive neuroectodermal tumor of bone: evaluation of increasing the dose intensity of chemotherapy--a report from the Children's Oncology Group.
abstract: BACKGROUND
  The outcome for patients with Ewing sarcoma family of tumors (ESFTs) of bone with metastases at diagnosis remains poor despite new approaches to treatment. We evaluated whether a dose-intensity chemotherapy regimen improved survival for patients with ESFTs of bone with metastases at diagnosis.
  
  
  METHODS
  We entered 60 patients with metastatic ESFTs of bone onto a single arm trial of a new intensive therapy. Treatment consisted of 51-weeks of chemotherapy and local control of the primary with radiation, surgery, or both. The chemotherapeutic protocol included two alternating blocks: one with vincristine (2 mg/m(2)), doxorubicin (90 mg/m(2)), and cyclophosphamide (2,200 mg/m(2)); and the second with ifosfamide (2,800 mg/m(2)/day x 5 days) and etoposide (100 mg/m(2)/day x 5 days).
  
  
  RESULTS
  Of the 60 patients with metastatic ESFTs of bone enrolled onto this single arm trial, 12 had metastasis to lung only, 7 to bone marrow or bone only, 38 to multiple sites, 2 in other sites and 3 not specified. There were three toxic deaths. Six patients (6-year cumulative incidence: 9%) developed second malignant neoplasms and died. The 6-year overall event-free survival (EFS) was 28% (standard error (SE) 6%) and survival (S) was 29% (SE 6%).
  
  
  CONCLUSIONS
  An intensified treatment regimen using higher doses of cyclophosphamide, ifosfamide, and doxorubicin increased toxicity and risk of second malignancy without improving EFS and S.
authors.affiliation: Division of Pediatrics, Department of Pediatric Hematology/Oncology, City of Hope National Medical Center, Duarte, California 91010, USA. jmiser@coh.org
authors.forename: James S
authors.initials: JS
authors.lastname: Miser
authors.forename: Robert E
authors.initials: RE
authors.lastname: Goldsby
authors.forename: Zhengjia
authors.initials: Z
authors.lastname: Chen
authors.forename: Mark D
authors.initials: MD
authors.lastname: Krailo
authors.forename: Nancy J
authors.initials: NJ
authors.lastname: Tarbell
authors.forename: Michael P
authors.initials: MP
authors.lastname: Link
authors.forename: Christopher J H
authors.initials: CJ
authors.lastname: Fryer
authors.forename: Douglas J
authors.initials: DJ
authors.lastname: Pritchard
authors.forename: Mark C
authors.initials: MC
authors.lastname: Gebhardt
authors.forename: Paul S
authors.initials: PS
authors.lastname: Dickman
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Perlman
authors.forename: Paul A
authors.initials: PA
authors.lastname: Meyers
authors.forename: Sarah S
authors.initials: SS
authors.lastname: Donaldson
authors.forename: Sheila G
authors.initials: SG
authors.lastname: Moore
authors.forename: Aaron R
authors.initials: AR
authors.lastname: Rausen
authors.forename: Teresa J
authors.initials: TJ
authors.lastname: Vietti
authors.forename: Holcombe E
authors.initials: HE
authors.lastname: Grier
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D001859:Bone Neoplasms / Q000175:diagnosis / Q000628:therapy*; D002648:Child; D002675:Child, Preschool; D003422:Critical Care; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D007279:Injections, Subcutaneous; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis / Q000628:therapy*; D016609:Neoplasms, Second Primary / Q000139:chemically induced* / Q000175:diagnosis; D018242:Neuroectodermal Tumors, Primitive / Q000175:diagnosis / Q000556:secondary / Q000628:therapy*; D012307:Risk Factors; D012512:Sarcoma, Ewing / Q000175:diagnosis / Q000556:secondary / Q000628:therapy*; D015996:Survival Rate; D016896:Treatment Outcome