title: Randomized controlled trial of interval-compressed chemotherapy for the treatment of localized Ewing sarcoma: a report from the Children's Oncology Group.
abstract: OBJECTIVE
  Chemotherapy with alternating vincristine-doxorubicin-cyclophosphamide and ifosfamide-etoposide cycles and primary tumor treatment with surgery and/or radiation therapy constitute the usual approach to localized Ewing sarcoma in North America. We tested whether chemotherapy intensification through interval compression could improve outcome.
  
  
  METHODS
  This was a prospective, randomized controlled trial for patients younger than 50 years old with newly diagnosed localized extradural Ewing sarcoma. Patients assigned to standard and intensified treatment were to begin chemotherapy cycles every 21 and 14 days, respectively, provided an absolute neutrophil count greater than 750×10(6)/L and a platelet count greater than 75×10(9)/L. Patients received vincristine (2 mg/m2), doxorubicin (75 mg/m2), and cyclophosphamide (1.2 g/m2) alternating with ifosfamide (9 g/m2) and etoposide (500 mg/m2) for 14 cycles, with filgrastim (5 mg/kg per day; maximum, 300 mg) between cycles. Primary tumor treatment (surgery, radiation, or both) was to begin at week 13 (after four cycles in the standard arm and six cycles in the intensified arm). The primary end point was event-free survival (EFS). The study is registered at ClinicalTrials.gov (identifier: NCT00006734).
  
  
  RESULTS
  Five hundred eighty-seven patients were enrolled and randomly assigned, and 568 patients were eligible, with 284 patients in each regimen. For all cycles, the median cycle interval for standard treatment was 21 days (mean, 22.45 days); for intensified treatment, the median interval was 15 days (mean, 17.29 days). EFS at a median of 5 years was 65% in the standard arm and 73% in the intensified arm (P=.048). The toxicity of the regimens was similar.
  
  
  CONCLUSIONS
  For localized Ewing sarcoma, chemotherapy administered every 2 weeks is more effective than chemotherapy administered every 3 weeks, with no increase in toxicity.
authors.affiliation: Division of Oncology, CTRB 10, The Children's Hospital of Philadelphia, University of Pennsylvania, 3501 Civic Center Blvd, Philadelphia, PA 19104, USA. rwomer@upenn.edu
authors.forename: Richard B
authors.initials: RB
authors.lastname: Womer
authors.forename: Daniel C
authors.initials: DC
authors.lastname: West
authors.forename: Mark D
authors.initials: MD
authors.lastname: Krailo
authors.forename: Paul S
authors.initials: PS
authors.lastname: Dickman
authors.forename: Bruce R
authors.initials: BR
authors.lastname: Pawel
authors.forename: Holcombe E
authors.initials: HE
authors.lastname: Grier
authors.forename: Karen
authors.initials: K
authors.lastname: Marcus
authors.forename: Scott
authors.initials: S
authors.lastname: Sailer
authors.forename: John H
authors.initials: JH
authors.lastname: Healey
authors.forename: John P
authors.initials: JP
authors.lastname: Dormans
authors.forename: Aaron R
authors.initials: AR
authors.lastname: Weiss
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D004334:Drug Administration Schedule; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage / Q000009:adverse effects; D007223:Infant; D008875:Middle Aged; D011446:Prospective Studies; D012512:Sarcoma, Ewing / Q000188:drug therapy* / Q000473:pathology; D014750:Vincristine / Q000008:administration & dosage / Q000009:adverse effects; D055815:Young Adult
chemical_list: D014750:Vincristine; D005047:Etoposide; D004317:Doxorubicin; D003520:Cyclophosphamide; D007069:Ifosfamide