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Ifosfamide, carboplatin, and etoposide (ICE) reinduction chemotherapy in a large cohort of children and adolescents with recurrent/refractory sarcoma: The Children's Cancer Group (CCG) experience§


  • Presented at the Joint Meeting of the International Society of Pediatric Oncology and the American Society of Pediatric Hematology/Oncology, September 1999, Montreal, Canada.

  • A complete listing of grant support for research conducted by CCG and POG before initiation of the COG grant in 2003 is available at

  • §

    Patrick Van Winkle and Anne Angiolillo should be considered as equal primary and first authors.



The prognosis for children with recurrent/refractory sarcomas is poor. We determined the overall response rate (ORR) and overall survival (OS) of children with recurrent/refractory sarcomas who were given ifosfamide, carboplatin, and etoposide (ICE) in three Children's Cancer Group (CCG) phase I/II trials.


Children with recurrent/refractory sarcoma were treated with ifosfamide (1,800 mg/m2/day on day 0–4), carboplatin (400 mg/m2/day on day 0–1), etoposide (100 mg/m2/day on day 0–4) and either rhG-CSF (10 μg/kg/day vs. 5 μg/kg/day, CCG-0894, 71 patients), PIXY321 (500–1,000 μg/m2/day, CCG-0924, 14 patients), or rhG-CSF (5 μg/kg/day) and IL-6 (2.5–5 μg/kg/day, CCG-0931, 12 patients).


Ninety-seven patients were evaluable for tumor response, 56 male and 41 female, median age 14.1 years (range 2.8–22.5 years). Tumor types were osteosarcoma (OTS) (n = 34), rhabdomyosarcoma (n = 27), Ewing sarcoma (EWS) (n = 21), soft tissue sarcoma-not otherwise specified (n = 5), undifferentiated sarcoma (n = 6), fibrosarcoma (n = 2), peripheral primitive neuroectodermal tumor (n = 1), and extraosseous Ewing (n = 1). The ORR was 51% (27% complete response [CR]). OS at 1 and 2 years was 49% and 28%, respectively. Patients with CR or partial response (PR) had significantly increased 1- and 2-year OS, 71% and 41%, respectively, (P < 0.001). Rhabdomyosarcoma patients with embryonal histology had significant improvement in 1- and 2-year OS: 82% and 46%, respectively, compared with other histologies, (P < 0.005).


The ORR to ICE reinduction chemotherapy in children with recurrent/refractory sarcoma was 51%. OS of 1 and 2 years appeared significantly improved in patients who had CR or PR following ICE reinduction therapy or who had rhabdomyosarcoma with embryonal histology. © 2004 Wiley-Liss, Inc.

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