The addition of ifosfamide and etoposide to the standard four-drug chemotherapy regimen for Ewing’s sarcoma significantly improves survival for patients with newly diagnosed, non-metastatic disease, according to an article in the February 20th issue of the New England Journal of Medicine.

A total of 518 patients diagnosed with Ewing’s sarcoma, primitive neuroectodermal tumor of bone, or primitive sarcoma of bone were enrolled and randomized to 49 weeks of standard chemotherapy (doxorubicin, vincristine, cyclophosphamide, and dactinomycin) or to the experimental treatment of standard therapy alternating with courses of ifosfamide and etoposide. Of the 120 patients with known metastatic disease, 62 were randomized to standard therapy and 58 to experimental treatment. Of the 398 patients with non-metastatic disease, 200 patients were randomized to standard therapy and 198 to experimental therapy.

Among patients with non-metastatic disease, there was a significant 5-year event-free survival advantage for patients on experimental therapy (69 percent versus 54 percent), as well as a significant advantage in overall survival (72 percent versus 61 percent). In contrast, there were no significant differences in survival rates for patients with metastatic disease.

The trial, which was conducted by members of two large North American pediatric cancer research groups, used an experimental therapy that had already proved successful in Ewing's sarcoma patients who had relapsed following standard therapy. Since the 5-year trial closed in 1992, the experimental regimen has become routine for patients with non-metastatic disease.

"It's the standard of care across the country now, and it has markedly improved the survival rate for a child with this disease," said lead author Holcombe E. Grier, M.D.

Ewing's sarcoma and primitive neuroectodermal tumor of bone, a closely related tumor, occur in children, adolescents, and young adults, but cases most often are diagnosed in teenagers. According to the American Cancer Society, Ewing's sarcoma and primitive neuroectodermal tumor of the bone account for approximately 5 percent of all childhood bone tumors in the United States, with an estimated 150 new cases diagnosed each year.

Factors other than type of chemotherapy that influenced event-free survival include age, tumor size, and tumor location. Patients typically had better outcomes if they were younger, had smaller tumors, or had tumors that were located in the distal regions of the arms and legs. Some ongoing studies are examining whether an increase in dose intensity of the agents used in this protocol can further improve survival in Ewing's sarcoma.

In an accompanying editorial, Robert E. Wittes, M.D., noted that the clinical trial was able to recruit more patients more rapidly than had been expected. He wrote that obtaining the results was "a major achievement."