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

J Clin Oncol. 2009 Nov 1;27(31):5182-8. doi: 10.1200/JCO.2009.22.3768. Epub 2009 Sep 21.


Purpose: 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).

Patients and 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.

Conclusion: For intermediate-risk RMS, VAC/VTC does not significantly improve FFS compared with VAC.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Child
  • Child, Preschool
  • Cyclophosphamide / administration & dosage
  • Cyclophosphamide / adverse effects
  • Dactinomycin / administration & dosage
  • Dactinomycin / adverse effects
  • Disease-Free Survival
  • Female
  • Humans
  • Infant
  • Kaplan-Meier Estimate
  • Male
  • Neoplasm Staging
  • Rhabdomyosarcoma / drug therapy*
  • Rhabdomyosarcoma / mortality
  • Rhabdomyosarcoma / pathology
  • Topotecan / administration & dosage
  • Topotecan / adverse effects
  • Vincristine / administration & dosage
  • Vincristine / adverse effects


  • Dactinomycin
  • Vincristine
  • Topotecan
  • Cyclophosphamide