Dose-intensified doxorubicin plus ifosfamide, vincristine, and dactinomycin (IVA) did not lead to any significant improvements in outcome among patients with high-risk non-metastatic rhabdomyosarcoma, according to a study published in The Lancet Oncology.1

Previous studies have demonstrated the efficacy of doxorubicin for the treatment of rhabdomyosarcoma, but its place in combination therapy with established treatment regimens such as IVA requires further investigation.

For this phase 3 study, researchers randomly assigned 484 patients aged between 6 months and 17 years to receive 9 cycles of IVA with or without doxorubicin. Intervals between each treatment cycle was 3 weeks. Patients were assigned to specific subgroups based on EpSSG stratification systems.

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After a median follow-up of 63.9 months, results showed that the 3-year event-free survival rate was 67.5% (95% CI, 61.2-73.1) among patients in the IVA plus doxorubicin arm compared with 63.3% among those who treated with IVA alone (hazard ratio [HR], 0.87; 95% CI, 0.65-1.16; P = .33).

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Patients treated with IVA and doxorubicin had significantly higher rates of grade 3 to 4 leukopenia (93% vs 85%; P = .0061), anemia (78% vs 49%; P < .0001), thrombocytopenia (67% vs 26%; P < .0001), gastrointestinal adverse events (31% vs 8%; P < .0001), and grade 3 to 5 infections (79% vs 56%; P < .0001) compared with patients treated with IVA alone. Two treatment-related deaths occurred among patients who received doxorubicin after the first cycle of treatment; no deaths were observed in the IVA alone group.

The authors concluded that “doxorubicin should be omitted from the first-line chemotherapy of patients with localized rhabdomyosarcoma, sparing them from significant acute toxic effects and late morbidity.”


  1. Bisogno G, Jenney M, Bergeron C, et al. Addition of dose-intensified doxorubicin to standard chemotherapy for rhabdomyosarcoma (EpSSG RMS 2005): a multicentre, open-label, randomised controlled, phase 3 trial [published online June 22, 2018]. Lancet Oncol. doi: 10.1016/S1470-2045(18)30337-1