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Treatment of Metastatic Ewing's Sarcoma or Primitive Neuroectodermal Tumor of Bone: Evaluation of Combination Ifosfamide and Etoposide—A Children's Cancer Group and Pediatric Oncology Group Study

From the Division of Pediatrics, Department of Pediatric Hematology/Oncology, City of Hope National Medical Center, Duarte; Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles; Department of Pediatrics and Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA; Dana-Farber Cancer Institute and Children's Hospital; the Department of Orthopedic Surgery, Children's Hospital; the Department of Radiation Oncology, Massachusetts General Hospital; the Departments of Pediatrics, Radiation Oncology, and Orthopedic Surgery, Harvard Medical School, Boston, MA; Mayo Clinic, Rochester, MN; Department of Pathology, Children's Hospital of Pittsburgh, Pittsburgh, PA; Department of Pathology, Johns Hopkins Hospital, Baltimore, MD; Memorial Sloan-Kettering Cancer Center; Department of Pediatrics, New York University Medical Center, New York, NY; Division of Pediatric Hematology/Oncology, Washington University Medical Center; the Department of Pediatrics, Washington University School of Medicine, St Louis, MO; and Department of Paediatrics, King Khalid National General Hospital, Jeddah, Kingdom of Saudi Arabia

Address reprint requests to James Miser, MD, City of Hope National Medical Center, 1500 E Duarte Rd, Duarte, CA 91010; e-mail: jmiser{at}coh.org

PURPOSE: One hundred twenty patients with metastatic Ewing's sarcoma or primitive neuroectodermal tumor (PNET) of bone were entered onto a randomized trial evaluating whether the addition of ifosfamide and etoposide to vincristine, doxorubicin, cyclophosphamide, and dactinomycin improved outcomes.

METHODS: Thirty-two patients had metastases to lungs only, 12 patients had metastases to bone marrow or bones only, 64 patients had metastases in multiple sites, and five patients had metastases in other sites; seven patients could not be assessed precisely. Treatment comprised 9 weeks of chemotherapy before local control and 42 weeks of chemotherapy; thereafter, regimen A consisted of vincristine 2 mg/m², cyclophosphamide 1,200 mg/m², and either doxorubicin 75 mg/m² or dactinomycin 1.25 mg/m². Regimen B consisted of regimen A alternating every 3 weeks with ifosfamide 1,800 mg/m²/d for 5 days and etoposide 100 mg/m²/d for 5 days.

RESULTS: Patients treated on regimen B did not have significantly better survival than those treated on regimen A. The event-free survival (EFS) and survival (S) at 8 years were 20% (SE, 5%) and 32% (SE, 6%), respectively, for those treated on regimen A and 20% (SE, 6%) and 29% (SE, 6%), respectively, for those treated on regimen B. Patients who had only lung metastases had EFS and S of 32% (SE, 8%) and 41% (SE, 9%), respectively, at 8 years. There were six toxic deaths (5%), four from cardiac toxicity and two from sepsis (four treated on regimen B and two treated on regimen A). Two had second malignant neoplasms.

CONCLUSION: Adding ifosfamide and etoposide to standard therapy does not improve outcomes of patients with Ewing's sarcoma or PNET of bone with metastases at diagnosis.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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