title: 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.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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 microg/kg/day vs. 5 microg/kg/day, CCG-0894, 71 patients), PIXY321 (500-1,000 microg/m2/day, CCG-0924, 14 patients), or rhG-CSF (5 microg/kg/day) and IL-6 (2.5-5 microg/kg/day, CCG-0931, 12 patients).
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Childrens Hospital of Los Angeles, Los Angeles, California, USA.
authors.forename: Patrick
authors.initials: P
authors.lastname: Van Winkle
authors.forename: Anne
authors.initials: A
authors.lastname: Angiolillo
authors.forename: Mark
authors.initials: M
authors.lastname: Krailo
authors.forename: Ying-Kuen
authors.initials: YK
authors.lastname: Cheung
authors.forename: Barry
authors.initials: B
authors.lastname: Anderson
authors.forename: Virginia
authors.initials: V
authors.lastname: Davenport
authors.forename: Gregory
authors.initials: G
authors.lastname: Reaman
authors.forename: Mitchell S
authors.initials: MS
authors.lastname: Cairo
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D002648:Child; D002675:Child, Preschool; D003115:Colony-Stimulating Factors / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D008297:Male; D015999:Multivariate Analysis; D016016:Proportional Hazards Models; D012008:Recurrence; D012208:Rhabdomyosarcoma / Q000188:drug therapy / Q000401:mortality; D012509:Sarcoma / Q000188:drug therapy* / Q000401:mortality; D015996:Survival Rate
chemical_list: D003115:Colony-Stimulating Factors; D005047:Etoposide; D016190:Carboplatin; D007069:Ifosfamide