Good Outcomes With Intensive, Interval-Compressed Chemotherapy and Irinotecan as Radiosensitizer in High-Risk Rhabdomyosarcoma


Key Points

  • Three-year rates were 69% for event-free survival and 79% for overall survival in patients with 0 or 1 Oberlin risk factors.
  • In very high–risk patients, 3-year event-free survival was 20%.

As reported in the Journal of Clinical Oncology by Weigel et al in the Children’s Oncology Group, a strategy of dose intensification and interval compression, use of the most active agents determined in phase II window studies, and use of irinotecan as a radiation sensitizer has been found to produce a remarkable 3-year event-free survival of 69% among patients with metastatic rhabdomyosarcoma and 0 or 1 Oberlin risk factors.

Study Details

In the study (ARST0431), patients received 54 weeks of therapy consisting of: blocks of vincristine/irinotecan (weeks 1–6, 20–25, and 47–52), interval compression with vincristine/doxorubicin/cyclophosphamide alternating with etoposide/ifosfamide (weeks 7–9 and 26–34), and vincristine/dactinomycin/cyclophosphamide (weeks 38–46). Radiation therapy was given at weeks 20 to 25 (primary) and was also permitted at weeks 1 to 6 (for intracranial or paraspinal extension) and weeks 47 to 52 (for extensive metastatic sites).

A total of 109 patients were enrolled. Patient age was < 1 year for 3%, 1 to 9 years for 35%, 10 to 20 years for 56%, and ≥ 21 years for 6%; 55% were male.


Median follow-up in surviving patients was 3.8 years. Among all patients, 3-year event-free survival was 38% (95% confidence interval [CI] = 29%–48%) and 3-year overall survival was 56% (95% CI = 46%–66%).

Among 43 patients with 1 or no Oberlin risk factors (age > 10 years or < 1 year, unfavorable primary site of disease, ≥ 3 metastatic sites, and bone or bone marrow involvement), 3-year rates were 69% (95% CI = 52%–82%) for event-free survival and 79% (62%–89%) for overall survival.

Among 66 patients with two or more risk factors, 3-year rates were 20% (95% CI = 11%–30%) for even-free survival and 14% (95% CI = 11%–18%) for overall survival.

Among 20 patients aged < 10 years with embryonal rhabdomyosarcoma, 3-year rates were 60% (95% CI = 36%–78%) for event-free survival and 79% (95% CI = 54%–92%) for overall survival.

Toxicity was similar to that reported in prior rhabdomyosarcoma studies.

As noted by the investigators, the finding among patients with 0 or 1 Oberlin risk factors compare well with 3-year relapse-free survival of 44% in a historical cohort.

The investigators concluded: “Patients with metastatic [rhabdomyosarcoma] with one or no Oberlin risk factor had an improved 3-year [event-free survival] of 69% [in the current study] compared with an historical cohort from pooled European and US studies; those with two or more risk factors have a dismal prognosis, and new approaches are needed for this very-high-risk group.”

Carola A.S. Arndt, MD, of Mayo Clinic, Rochester, is the corresponding author for the Journal of Clinical Oncology article.

The study was supported by Children’s Oncology Group grants. For full disclosures of the study authors, visit

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.