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Previous Volume 348:694-701 February 20, 2003 Number 8 Next

	Full Text PDF PDA Full Text PowerPoint Slide Set Editorial by Wittes, R. E. Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited E-mail When Letters Appear PubMed Citation

ABSTRACT

Background Ewing's sarcoma and primitive neuroectodermal tumor of bone are closely related, highly malignant tumors of children, adolescents, and young adults. A new drug combination, ifosfamide and etoposide, was highly effective in patients with Ewing's sarcoma or primitive neuroectodermal tumor of bone who had a relapse after standard therapy. We designed a study to test whether the addition of these drugs to a standard regimen would improve the survival of patients with newly diagnosed disease.

Methods Patients 30 years old or younger with Ewing's sarcoma, primitive neuroectodermal tumor of bone, or primitive sarcoma of bone were eligible. The patients were randomly assigned to receive 49 weeks of standard chemotherapy with doxorubicin, vincristine, cyclophosphamide, and dactinomycin or experimental therapy with these four drugs alternating with courses of ifosfamide and etoposide.

Results A total of 518 patients met the eligibility requirements. Of 120 patients with metastatic disease, 62 were randomly assigned to the standard-therapy group and 58 to the experimental-therapy group. There was no significant difference in five-year event-free survival between the treatment groups (P=0.81). Among the 398 patients with nonmetastatic disease, the mean (±SE) five-year event-free survival among the 198 patients in the experimental-therapy group was 69±3 percent, as compared with 54±4 percent among the 200 patients in the standard-therapy group (P=0.005). Overall survival was also significantly better among patients in the experimental-therapy group (72±3.4 percent vs. 61±3.6 percent in the standard-therapy group, P=0.01).

Conclusions The addition of ifosfamide and etoposide to a standard regimen does not affect the outcome for patients with metastatic disease, but it significantly improves the outcome for patients with nonmetastatic Ewing's sarcoma, primitive neuroectodermal tumor of bone, or primitive sarcoma of bone.

Source Information

From the Departments of Pediatric Hematology and Oncology, Dana–Farber Cancer Institute and Children's Hospital, Boston (H.E.G.); Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles (M.D.K.); Radiation Oncology, Massachusetts General Hospital, Boston (N.J.T.); Pediatrics (H.E.G.), Radiation Oncology (N.J.T.), and Orthopedic Surgery (M.C.G.), Harvard Medical School, Boston; Pediatrics (M.P.L.) and Radiation Oncology (S.S.D.), Stanford University School of Medicine, Stanford, Calif.; Pediatrics, King Khalid National Hospital, Jeddah, Saudi Arabia (C.J.H.F.); the Mayo Clinic, Rochester, Minn. (D.J.P.); Orthopedic Surgery, Children's Hospital, Boston (M.C.G.); Pathology, Children's Hospital of Pittsburgh, Pittsburgh (P.S.D.); Pathology, Johns Hopkins Hospital, Baltimore (E.J.P.); Memorial Sloan-Kettering Cancer Center, New York (P.A.M.); Keck School of Medicine, University of Southern California, and Radiology, Children's Hospital of Los Angeles — both in Los Angeles (S.M.); Pediatrics, New York University Medical Center, New York (A.R.R.); the Division of Pediatric Hematology and Oncology, Washington University Medical Center, and Pediatrics, Washington University School of Medicine, St. Louis (T.J.V.); and Pediatrics, City of Hope National Medical Center, Duarte, Calif. (J.S.M.).

Address reprint requests to Dr. Grier at the Dana–Farber Cancer Institute, 44 Binney St., Boston, MA 02115, or at holcombe_grier{at}dfci.harvard.edu.

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