Journal of Clinical Oncology, Vol 10, 1737-1742, Copyright © 1992 by American Society of Clinical Oncology

ARTICLES

Ifosfamide plus etoposide in newly diagnosed Ewing's sarcoma of bone

WH Meyer, L Kun, N Marina, P Roberson, D Parham, B Rao, B Fletcher and CB Pratt
Department of Hematology-Oncology, St Jude Children's Research Hospital, Memphis, TN 38101-0318.

PURPOSE: We assessed the activity of ifosfamide plus etoposide against newly diagnosed Ewing's sarcoma of bone by administering this drug pair before standard induction therapy (the upfront window approach). PATIENTS AND METHODS: Twenty-six children and adolescents with newly diagnosed, previously untreated Ewing's sarcoma of bone were enrolled onto this pilot study (EW-87). Eighteen were at a higher risk of treatment failure, with a primary tumor size of more than 8 cm or metastases at diagnosis. Window therapy with ifosfamide (1.6 g/m2/d with mesna uroprotection) and etoposide (100 mg/m2/d) was given in three 5-day cycles at 21-day intervals. Responses were evaluated clinically and radiologically. Subsequent induction therapy comprised three cycles of cyclophosphamide and doxorubicin. Radiation therapy was the primary local control modality; surgery was limited to biopsy or resection of expendable bones. After the local control phase, alternating courses of vincristine plus dactinomycin, ifosfamide plus etoposide, and cyclophosphamide plus doxorubicin were given as maintenance therapy. RESULTS: There were four complete responses and 21 partial responses to ifosfamide/etoposide window therapy (overall response rate 96%; 95% confidence interval [CI], 80% to 99%). Disease progression was observed in four patients during the cyclophosphamide/doxorubicin phase. Chemotherapy was well tolerated; only 16% (20 of 125) of all ifosfamide/etoposide window and maintenance cycles resulted in hospitalization for fever and neutropenia. Two patients developed chemotherapy-induced cystitis. CONCLUSIONS: The combination of ifosfamide and etoposide is highly active against previously untreated Ewing's sarcoma and generally is well tolerated. The ultimate impact of these two agents on outcome will be determined in randomized multicenter studies.

This article has been cited by other articles:

				C. Rodriguez-Galindo, F. Navid, T. Liu, C. A. Billups, B. N. Rao, and M. J. Krasin Prognostic factors for local and distant control in Ewing sarcoma family of tumors Ann. Onc., April 1, 2008; 19(4): 814 - 820. [Abstract] [Full Text] [PDF]

				H. S. Hosalkar and J. P. Dormans Surgical Management of Pelvic Sarcoma in Children J. Am. Acad. Ortho. Surg., July 1, 2007; 15(7): 408 - 424. [Abstract] [Full Text] [PDF]

				O. Oberlin, A. Rey, A. S. Desfachelles, T. Philip, D. Plantaz, C. Schmitt, E. Plouvier, O. Lejars, H. Rubie, P. Terrier, et al. Impact of High-Dose Busulfan Plus Melphalan As Consolidation in Metastatic Ewing Tumors: A Study by the Societe Francaise des Cancers de l'Enfant J. Clin. Oncol., August 20, 2006; 24(24): 3997 - 4002. [Abstract] [Full Text] [PDF]

				M. Bernstein, H. Kovar, M. Paulussen, R. L. Randall, A. Schuck, L. A. Teot, and H. Juergensg Ewing's Sarcoma Family of Tumors: Current Management. Oncologist, May 1, 2006; 11(5): 503 - 519. [Abstract] [Full Text] [PDF]

				S.J. Strauss, A. McTiernan, D. Driver, M. Hall-Craggs, A. Sandison, A.M. Cassoni, A. Kilby, M. Michelagnoli, J. Pringle, J. Cobb, et al. Single Center Experience of a New Intensive Induction Therapy for Ewing's Family of Tumors: Feasibility, Toxicity, and Stem Cell Mobilization Properties J. Clin. Oncol., August 1, 2003; 21(15): 2974 - 2981. [Abstract] [Full Text] [PDF]

				H. E. Grier, M. D. Krailo, N. J. Tarbell, M. P. Link, C. J.H. Fryer, D. J. Pritchard, M. C. Gebhardt, P. S. Dickman, E. J. Perlman, P. A. Meyers, et al. Addition of Ifosfamide and Etoposide to Standard Chemotherapy for Ewing's Sarcoma and Primitive Neuroectodermal Tumor of Bone N. Engl. J. Med., February 20, 2003; 348(8): 694 - 701. [Abstract] [Full Text] [PDF]

				B. H. Kushner and P. A. Meyers How Effective Is Dose-Intensive/Myeloablative Therapy Against Ewing's Sarcoma/Primitive Neuroectodermal Tumor Metastatic to Bone or Bone Marrow? The Memorial Sloan-Kettering Experience and a Literature Review J. Clin. Oncol., February 1, 2001; 19(3): 870 - 880. [Abstract] [Full Text] [PDF]

				S. L. Spunt, A. S. Pappo, and N. J. Winick Cyclophosphamide and Etoposide for Pediatric Solid Tumors J. Clin. Oncol., November 1, 2000; 18(21): 3741 - 3743. [Full Text] [PDF]

				S.J. Cotterill, S. Ahrens, M. Paulussen, H.F. Jurgens, P.A. Voute, H. Gadner, and A.W. Craft Prognostic Factors in Ewing's Tumor of Bone: Analysis of 975 Patients From the European Intergroup Cooperative Ewing's Sarcoma Study Group J. Clin. Oncol., September 17, 2000; 18(17): 3108 - 3114. [Abstract] [Full Text] [PDF]

				E. Mantadakis, L. Herrera, P. J. Leavey, R. O. Bash, N. J. Winick, and B. A. Kamen Fractionated Cyclophosphamide and Etoposide for Children With Advanced or Refractory Solid Tumors: A Phase II Window Study J. Clin. Oncol., July 1, 2000; 18(13): 2576 - 2581. [Abstract] [Full Text] [PDF]

				N. M. Marina, A. S. Pappo, D. M. Parham, A. M. Cain, B. N. Rao, C. A. Poquette, C. B. Pratt, C. Greenwald, and W. H. Meyer Chemotherapy Dose-Intensification for Pediatric Patients With Ewing's Family of Tumors and Desmoplastic Small Round-Cell Tumors: A Feasibility Study at St. Jude Children's Research Hospital J. Clin. Oncol., January 1, 1999; 17(1): 180 - 180. [Abstract] [Full Text] [PDF]

				M. Smith, J. Abrams, E. L. Trimble, and R. S. Ungerleider Dose Intensity of Chemotherapy for Childhood Cancers Oncologist, October 1, 1996; 1(5): 293 - 304. [Abstract] [Full Text] [PDF]

				Chest Wall Resection for Ewing's Sarcoma of the Rib: An Unnecessary Procedure Ann. Thorac. Surg., November 1, 1995; 60(5): 1454 - 1454. [Full Text]