title: Prospective randomized trial between two doses of granulocyte colony-stimulating factor after ifosfamide, carboplatin, and etoposide in children with recurrent or refractory solid tumors: a children's cancer group report.
abstract: OBJECTIVE
  The objectives of this study were: 1) to compare the time to hematologic recovery (absolute neutrophil count [ANC] > or = 1,000/mm3 and platelet count > or = 100,000/mm3) in a randomized prospective study of two doses of granulocyte colony-stimulating factor (G-CSF) (5.0 vs. 10.0 microg/kg per day) after ifosfamide, carboplatin, and etoposide (ICE) chemotherapy; and 2) to determine the response rate (complete response [CR] + partial response [PR]) of ICE in children with refractory or recurrent solid tumors.
  
  
  METHODS
  From June 1992 until November 1994, 123 patients with recurrent or refractory pediatric solid tumors were treated with ifosfamide (1,800 mg/m2 per day x 5), carboplatin (400 mg/m2 per day x 2), and etoposide (100 mg/m2 per day x 5) and randomized to receive either 5.0 microg/kg per day or 10.0 microg/kg per day of G-CSF subcutaneously until recovery of ANC to > or = 1,000/mm3.
  
  
  RESULTS
  The incidence of grade 4 neutropenia during the first course was 88%. Median time from the start of chemotherapy to ANC > or = 1,000/mm(-3) for all patients during courses 1 and 2 was 21 and 19 days, respectively. The incidence of developing platelet count < or = 20,000/mm3 during course 1 was 82%. The median time from the start of the course of chemotherapy to platelet recovery > or =100,000/mm3 for all patients during courses 1 and 2 was 27 days. There was no significant difference in the median time of ANC recovery, platelet recovery, or incidence of grade 4 neutropenia; and in the median days of fever and the incidence of infections requiring hospitalization and intravenous antibiotics during courses 1 and 2, there was no significant difference between the two doses of G-CSF. One hundred eighteen patients were evaluated for response to ICE. The overall response rate (CR + PR) in this study was 51% (90% confidence interval, 43%-59%). The CR rate for all diagnostic categories was 27%. The Kaplan-Meier estimates of 1-year and 2-year survival probabilities for all patients were 52% and 30%, respectively.
  
  
  CONCLUSIONS
  In summary, this combination of chemotherapy (ICE) was associated with a high CR rate (27%) in children with recurrent or refractory solid tumors, but also with a high incidence of grade 4 neutropenia and thrombocytopenia. Doubling the dose of G-CSF from 5.0 to 10.0 microg/kg per day after ICE chemotherapy did not result in an enhancement of neutrophil or platelet recovery or the incidence of grade 4 neutropenia developing.
authors.affiliation: Babies and Children's Hospital, Columbia University, New York, New York, USA. MC1310@columbia.edu
authors.forename: M S
authors.initials: MS
authors.lastname: Cairo
authors.forename: V
authors.initials: V
authors.lastname: Shen
authors.forename: M D
authors.initials: MD
authors.lastname: Krailo
authors.forename: M
authors.initials: M
authors.lastname: Bauer
authors.forename: J S
authors.initials: JS
authors.lastname: Miser
authors.forename: J K
authors.initials: JK
authors.lastname: Sato
authors.forename: J
authors.initials: J
authors.lastname: Blatt
authors.forename: B R
authors.initials: BR
authors.lastname: Blazar
authors.forename: S
authors.initials: S
authors.lastname: Frierdich
authors.forename: W
authors.initials: W
authors.lastname: Liu-Mares
authors.forename: G H
authors.initials: GH
authors.lastname: Reaman
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D007223:Infant; D007958:Leukocyte Count; D008297:Male; D009369:Neoplasms / Q000188:drug therapy* / Q000401:mortality; D009503:Neutropenia / Q000209:etiology* / Q000517:prevention & control; D009504:Neutrophils; D011446:Prospective Studies; D044469:Racial Groups; D011994:Recombinant Proteins; D012008:Recurrence; D015996:Survival Rate; D013997:Time Factors; D014481:United States
chemical_list: D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D005047:Etoposide; D016190:Carboplatin; D007069:Ifosfamide