title: Vincristine, actinomycin, and cyclophosphamide compared with vincristine, actinomycin, and cyclophosphamide alternating with vincristine, topotecan, and cyclophosphamide for intermediate-risk rhabdomyosarcoma: children's oncology group study D9803.
abstract: OBJECTIVE
  The purpose of this study was to compare the outcome of patients with intermediate-risk rhabdomyosarcoma (RMS) treated with standard VAC (vincristine, dactinomycin, and cyclophosphamide) chemotherapy to that of patients treated with VAC alternating with vincristine, topotecan, and cyclophosphamide (VAC/VTC).
  
  
  METHODS
  Patients were randomly assigned to 39 weeks of VAC versus VAC/VTC; local therapy began after week 12. Patients with parameningeal RMS with intracranial extension (PME) were treated with VAC and immediate x-ray therapy. The primary study end point was failure-free survival (FFS). The study was designed with 80% power (5% two-sided alpha level) to detect an increase in 5-year FFS from 64% to 75% with VAC/VTC.
  
  
  RESULTS
  A total of 617 eligible patients were entered onto the study: 264 were randomly assigned to VAC and 252 to VAC/VTC; 101 PME patients were nonrandomly treated with VAC. Treatment strata were embryonal RMS, stage 2/3, group III (33%); embryonal RMS, group IV, less than age 10 years (7%); alveolar RMS or undifferentiated sarcoma (UDS), stage 1 or group I (17%); alveolar RMS/UDS (27%); and PME (16%). At a median follow-up of 4.3 years, 4-year FFS was 73% with VAC and 68% with VAC/VTC (P = .3). There was no difference in effect of VAC versus VAC/VTC across risk groups. The frequency of second malignancies was similar between the two treatment groups.
  
  
  CONCLUSIONS
  For intermediate-risk RMS, VAC/VTC does not significantly improve FFS compared with VAC.
authors.affiliation: Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, MN 55905, USA. carndt@mayo.edu
authors.forename: Carola A S
authors.initials: CA
authors.lastname: Arndt
authors.forename: Julie A
authors.initials: JA
authors.lastname: Stoner
authors.forename: Douglas S
authors.initials: DS
authors.lastname: Hawkins
authors.forename: David A
authors.initials: DA
authors.lastname: Rodeberg
authors.forename: Andrea A
authors.initials: AA
authors.lastname: Hayes-Jordan
authors.forename: Charles N
authors.initials: CN
authors.lastname: Paidas
authors.forename: David M
authors.initials: DM
authors.lastname: Parham
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Teot
authors.forename: Moody D
authors.initials: MD
authors.lastname: Wharam
authors.forename: John C
authors.initials: JC
authors.lastname: Breneman
authors.forename: Sarah S
authors.initials: SS
authors.lastname: Donaldson
authors.forename: James R
authors.initials: JR
authors.lastname: Anderson
authors.forename: William H
authors.initials: WH
authors.lastname: Meyer
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D002648:Child; D002675:Child, Preschool; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D003609:Dactinomycin / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007223:Infant; D053208:Kaplan-Meier Estimate; D008297:Male; D009367:Neoplasm Staging; D012208:Rhabdomyosarcoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D019772:Topotecan / Q000008:administration & dosage / Q000009:adverse effects; D014750:Vincristine / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D003609:Dactinomycin; D014750:Vincristine; D019772:Topotecan; D003520:Cyclophosphamide