New drug combination improves survival in rare, aggressive bone cancer of children and young adults:

Adding two experimental drugs to the standard four-drug chemotherapy regimen has significantly improved survival in patients with nonmetastatic Ewing’s sarcoma, a highly malignant bone cancer of children and young adults, according to a report published in the Feb. 20 issue of the New England Journal of Medicine.

The large multi-institutional trial led by Holcombe E. Grier of Dana-Farber Cancer Institute and Boston Children’s Hospital, showed that the overall survival rate increased from 61 percent to 72 percent for Ewing’s sarcoma patients with localized disease who underwent the experimental six-drug chemotherapy.

Conducted by members of two large North American pediatric cancer research groups, the trial used an experimental therapy that had already proved successful in Ewing’s sarcoma patients who had relapsed following standard therapy. The five-year trial closed in 1992 and since then the experimental regimen has become routine for patients without metastases.

“It’s the standard of care across the country now, and it has markedly improved the survival rate for a child with this disease,” says Grier, who is associate professor of pediatrics at the Medical School.

Ewing’s sarcoma and primitive neuroectodermal tumor of bone, a closely related subgroup, strike children, adolescents, and young adults but 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.

Surgery and radiation therapy alone cure only a small proportion of patients. Beginning in the early 1970s, the use of adjuvant chemotherapy consisting of doxorubicin, cyclophosphamide, vincristine, and dactinomycin improved patients’ outcomes.

The trial conducted by Grier and his colleagues included 518 patients, of whom 120 had metastatic disease. Standard chemotherapy treatment was given every three weeks over a period of 49 weeks to 262 patients, while 256 patients received the standard treatment alternating with the experimental drugs, ifosfamide and etoposide.

There was no survival benefit for the patients whose cancer had spread at the time of diagnosis. However, the majority of patients did not have metastases at diagnosis. Patients without metastases who received the experimental therapy had an overall survival rate 18 percent higher (72 percent) than for those who received standard care (61 percent). “Overall survival” includes patients who remain alive but in some cases may have experienced a relapse. Using a more restrictive measure, the researchers found that 69 percent of the experimental group compared with 54 percent of the standard regimen group survived at least five years without relapse – a 28 percent improvement. Other factors influencing event-free survival included age, tumor size, and tumor location. Patients typically fared better if they were younger, had smaller tumors, or had tumors that were located in the arms and legs and well away from the pelvis. More recent studies investigate whether increasing the dose intensity of the agents used in this protocol can further improve survival in Ewing’s sarcoma.