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Multi-Agent, Dose-Intensive Regimen Improves EFS in Rhabdomyosarcoma

News | October 30, 2015 | Sarcoma, Radiation Oncology By Cancer Network Staff
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A treatment strategy including dose intensification with interval compression, use of the most active agents available, and the use of irinotecan as a radiation sensitizer led to a promising event-free survival (EFS) rate in children and young adult patients with metastatic rhabdomyosarcoma (RMS) who had one or no Oberlin risk factor, according to a report from the Children’s Oncology Group. High-risk patients had poorer results, and other treatment options are still likely needed.

“Although improvements in treatment strategies for patients with localized RMS have occurred over the past 3 decades by decreasing toxicity without compromising cure, little progress has been made in curing patients with metastatic disease,” wrote study authors led by Carola A. S. Arndt, MD, of the Mayo Clinic in Rochester, Minnesota. Previous phase II window studies have identified agents with the most activity, including ifosfamide/etoposide and vincristine/doxorubicin/cyclophosphamide, with irinotecan helping to sensitive patients to radiation therapy.

The new study included 109 patients, most aged 20 or younger (94%). Patients underwent a 54-week chemotherapy treatment regimen involving those agents and radiation in varying sequences, including interval compression to intensify doses. The results were published online ahead of print in the Journal of Clinical Oncology.

The study had a median follow-up for surviving patients of 3.8 years. The 3-year EFS rate was 38%, and the overall survival rate was 56%.

There were better results in patients with one or no Oberlin risk factors—these include age older than 10 years or younger than 1 year, unfavorable primary site of disease, at least three metastatic sites, and bone or bone marrow involvement. Those with one or none of those factors had a 3-year EFS rate of 69%, compared to only 20% for those with two or more such risk factors.

When compared with earlier studies in RMS patients, those in the new study with embryonal RMS showed an improved EFS, while other patients had similar outcomes to earlier research. The authors noted that toxicity in the new trial was also similar to previous research in this patient population.

The researchers concluded that these results show the lower-risk patients can have improved outcomes compared with previous studies when using this dose-intensive, multi-agent regimen including irinotecan given during radiation. “Different approaches are needed for the remainder of the high-risk patients with alveolar RMS who do not benefit from current treatment strategies,” they wrote.