Purpose: Intergroup Rhabdomyosarcoma Study Group (IRSG) studies III and IV showed improved failure-free survival (FFS) rates with vincristine, dactinomycin, and cyclophosphamide (VAC; total cumulative cyclophosphamide dose, 26.4 g/m(2)) compared with vincristine and dactinomycin (VA) for patients with subset-one low-risk embryonal rhabdomyosarcoma (ERMS; stage 1/2 group I/II ERMS or stage 1 group III orbit ERMS). The objective of Children's Oncology Group ARST0331 was to reduce the length of therapy without compromising FFS for this subset of low-risk patients by using VA in combination with lower-dose cyclophosphamide (total cumulative dose, 4.8 g/m(2)) plus radiotherapy (RT).
Patients and methods: This noninferiority prospective clinical trial enrolled newly diagnosed patients with subset-one clinical features. Therapy included four cycles of VAC followed by four cycles of VA over 22 weeks. Patients with microscopic or gross residual disease at study entry received RT.
Results: With a median follow-up of 4.3 years, we observed 35 failures among 271 eligible patients versus 48.4 expected failures, calculated using a fixed outcome based on the FFS expected for similar patients treated on the IRSG D9602 protocol. The estimated 3-year FFS rate was 89% (95% CI, 85% to 92%), and the overall survival rate was 98% (95% CI, 95% to 99%). Patients with paratesticular tumors had the most favorable outcome. Three-year cumulative incidence rates for any local, regional, or distant failures were 7.6%, 1.5%, and 3.4%, respectively.
Conclusion: Shorter-duration therapy that included lower-dose cyclophosphamide and RT did not compromise FFS for patients with subset-one low-risk ERMS.
© 2014 by American Society of Clinical Oncology.