Novel Combination Chemotherapy for Localized Ewing Sarcoma
Name of the Trial
Phase III Randomized Study of Adding Vincristine Sulfate, Topotecan Hydrochloride, and Cyclophosphamide to Standard Chemotherapy in Patients with Non-Metastatic Extracranial Ewing Sarcoma (COG-AEWS1031). See the protocol summary.
Dr. Mason Bond, Children’s Oncology Group (COG)
Why This Trial Is Important
Ewing sarcoma is a rare cancer of the bone or soft tissue that occurs primarily in adolescents and young adults. In fact, it is the second most common malignant bone tumor diagnosed in patients younger than 20 years of age. Most Ewing sarcomas have a characteristic chromosomal alteration that results in the expression of a fusion protein (EWS-FLI1) that inappropriately turns on cell-growth-promoting genes. Thus, these tumors tend to grow rapidly and often metastasize to the lung, bone, or bone marrow. The presence of metastases at diagnosis and being diagnosed at an older age are associated with a poorer prognosis.
Treatment for patients with Ewing sarcoma includes surgery, radiotherapy, or both, along with systemic chemotherapy. Until the introduction of combination chemotherapy, the 3- to 5-year survival rate for patients with Ewing sarcoma was less than 10 percent. However, results from several clinical trials have demonstrated improved survival for patients without metastases who were treated with a chemotherapy combination called VDC-IE, in which administration of the drugs vincristine, doxorubicin, and cyclophosphamide (VDC) is alternated with administration of the drugs ifosfamide and etoposide (IE), and by reducing the interval between cycles of VDC-IE.
In this clinical trial, which is being conducted in the United States, Canada, and Australia, researchers will test whether the addition of the drug combination vincristine, topotecan, and cyclophosphamide (VTC) to VDC-IE improves overall survival and event-free survival (survival without cancer progression or recurrence) in newly diagnosed patients with non-metastatic Ewing sarcoma of the bone or soft tissue (excluding the soft tissue of the skull). Eligible patients will be randomly assigned to receive six cycles of VDC-IE or VTC-IE-VDC followed by surgery, radiation therapy, or both and 11 more cycles of the initial chemotherapy.
“Because topotecan and cyclophosphamide are active in patients when Ewing sarcoma recurs or relapses, our thinking is that the combination may contribute to improving survival or preventing relapse in newly diagnosed patients,” said Dr. Leo Mascarenhas, vice chair of the trial.
“This trial is unique in that it is the first COG trial available through NCI’s Cancer Trials Support Unit (CTSU) that will enroll both adolescents and young adults,” added Dr. Mascarenhas. “It provides broader access to patients who may not be treated at a pediatric center, which is the case for a significant number of patients with Ewing sarcoma.”
Secondary aims of the trial include assessing the importance of initial tumor volume, tumor histology, and response to treatment as measured by PET scans as prognostic factors for localized Ewing tumors. Additionally, the effect of the type of local therapy (surgery, radiotherapy, or both) on associated complications and survival will be evaluated. “There are a lot of issues we hope to address in this trial to help us understand this disease better to improve the outcome of patients,” said Dr. Mascarenhas.